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Salmonella disrupts lymph node architecture

Scientists at Duke University Medical Center have gotten to the root of the damage that the deadly Salmonella bacterium does when it kills mice: the bacteria attack lymph nodes, where immune responses, including antibodies, are raised.

The finding may also be true for humans who suffer from the infection, said senior researcher Soman Abraham, about the work published in Nature Medicine online this week.

"Salmonella quickly gets into the draining lymph node, which is unfortunate because the nodes are what the immune system uses to combat bacteria" said Soman Abraham, Ph.D., a Duke professor of pathology, immunology, and molecular genetics and microbiology. "A lymph node has a specific architecture that allows immune cell types that are capable of recognizing pathogens like bacteria to enter and interact in particular parts of the node. This way the pathogen-specific cells can identify the pathogen and create just the right antibody." Once in the lymph node, Salmonella disrupts this underlying organization.

A Salmonella infection commonly arrives through infected food and sometimes from pets, like turtles.

Abraham said that Salmonella causes "chaotic responses" in the lymph nodes and shuts the nodes down, and the damage is even visible in the microscope images his laboratory captured. "The chaos that results is how Salmonella grows without stopping in mice. We suspect there is a similar scenario in humans."

This is the first proven case of a bacterium targeting lymph nodes and altering the architecture, to effectively shut down the immune response, Abraham said.

He said would like to study the Yersinia pestis bacteria, the pathogen responsible for the Bubonic plague (which killed so many people in the 14th Century), which also infects the lymph nodes, to see if it uses the same type of attack.

The findings from Duke suggest targets for therapies to relieve the suffering of those with Salmonella. "Another tactic would be to find a way to prevent Salmonella from getting into the nodes in the first place, because once they get in, they start this destruction" Abraham said.

Dr. Abraham did the research with co-author Ashley St. John, a graduate student in immunology at Duke, now at the Duke-NUS (National University of Singapore) Graduate Medical School, Singapore. The study was funded by the National Institutes of Health.

Further reading: Microbiology publications

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Microbiology Conferences and Meetings

Microbiology Conference List
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Microbiology conferences 2010


February 14 - 19, 2010 Antibiotics and Resistance: Challenges and Solutions
Santa Fe, NM, USA Further information
In the face of a growing crisis in antibiotic resistance and the emergence of new bacterial pathogens, there is a pressing clinical need for new antibiotics. Paradoxically, this call for new drugs comes at a time when investment in antibiotic development in the pharmaceutical industry is at historically low levels. Despite the promise of the genomic revolution to inform drug development and innovations in drug discovery and the fundamental biology that underpins it, modern control of infectious disease with antibiotics is perilously fragile. This meeting brings together researchers from medicine, academe and industry and from across scientific disciplines to discuss the challenges of antibiotic development in the 21st Century. What is the scope of the problem? What are possible solutions? What are the imperatives for the short and long term and is the traditional antibiotic paradigm in need of an overhaul? These questions will be the focus of the meeting that will help to define the problems and solutions in antibiotic development.
Suggested reading: Microbiology Books

February 16 - 21, 2010 Cell Biology of Virus Entry, Replication and Pathogenesis
Taos, NM, Canada Further information
The Keystone Symposia meeting on the Cell Biology of Virus Entry, Replication and Pathogenesis emphasizes key aspects of virus infection pathways and cellular responses. A central goal is the identification of critical virus-cell crosstalk during these processes. Rather than dividing viruses into separate “categories” such as positive-sense RNA viruses and DNA viruses, the meeting highlights common aspects of virus lifecycles among different virus groups. The multi-disciplinary nature of the proposed meeting is important in bringing together investigators using structural, molecular, cell biological, immunological and epidemiological methods. This emphasis on shared themes and multiple experimental approaches will continue to be critical to future advances in virology. While there has been spectacular recent progress in our understanding of virus lifecycles, we are still very far from being able to design antiviral strategies, and unexpected novel aspects of virus cell biology are constantly being discovered. Plenary sessions will cover the most important aspects of virus interactions with cells. Day 1 will include cutting-edge structural virology studies and imaging methods to follow single virus particles during entry. Day 2 will focus on the entry mechanisms of enveloped and non-enveloped viruses and the roles of cellular proteins in virus infection. Day 3 will cover viral and cellular aspects of virus replication and cellular antiviral responses. The last day will focus on the important areas of virus assembly and pathogenesis. Late-breaking exciting developments in this fast-moving field will be incorporated by short presentations and afternoon workshop sessions drawn from the submitted abstracts.
Suggested reading: Virology Books

February 18 - 19, 2010 Invasive Fungal Infections
Rome, Italy Further information
ESCMID Conference. Participants attending this conference will learn about the microbiological aspects, pathophysiology and clinical presentations of common and emerging invasive fungal infections. Up-to-date information on diagnosis and treatment for these infections will also be discussed in detail and future prospects will be highlighted.
Suggested reading: Mycology Books

February 21 - 24, 2010 ASM Biodefense and Emerging Diseases Research Meeting
Baltimore, MD, USA Further information
The purpose of this meeting is to bring together individuals who are carrying out research to defend against the growing threat of bioterrorism and decision makers shaping the future biodefense research agenda, recognizing that emerging infectious diseases serve as a paradigm for handling the public threat of bioterrorism.

February 23 - 26, 2010 Virus-host: partners in pathogenicity
San Jose, Costa Rica Further information
By necessity, viruses must resort to host cells for their amplification, since they rely on the host machineries for the synthesis of their proteins and efficient multiplication of their genome. EMBO World Lecture Courses
Suggested reading: Virology Books

February 26 - 26, 2010 The Bacteriophage in Biology, Biotechnology and Medicine
Welwyn Garden City, UK Further information
This meeting is the third in a successful biennial series discussing the biological nature of bacteriophages, and their exploitation in basic microbiology (for genetics and functional genomics); diagnostics, ecology and evolution, phage display, vaccines, and in therapeutics in animal and human infections. The general structure of the meeting is to have short, expert presentations on this spectrum of topics, plus short Q and A sessions and offered posters. The meeting will be of interest to anyone who is currently using phages in their research work or who might be interested in the potential application of phages for basic biology, and applied topics such as bacterial diagnostics, vaccine development and phage therapy
Suggested reading: Bacteriophage: Genetics and Molecular Biology

February 27 - March 5, 2010 ATP-Binding Cassette (ABC) Proteins: From Multidrug Resistance to Genetic Diseases
Innsbruck, Austria Further information
3rd FEBS Special Meeting on ABC Proteins - ABC2010 ABC2010 will cover all basic and applied aspects of ABC proteins, both in normal and cancer cells, as well as their important roles in genetic diseases as well as drug resistance phenomena in cancer or microbial systems. Leading scientists from all over the world and representatives of major pharmaceutical companies will present and discuss latest news on ABC proteins operating in bacteria, fungi, plants, parasites and humans. We were able to commit numerous leading experts to participate, with many new faces attending as plenary speakers.
Suggested reading: ABC Transporters in Microorganisms

March 2010


March 9 - 12, 2010 14th International Congress on Infectious Diseases (14th ICID)
Miami, FL, USA Further information
Organized by the International Society for Infectious Diseases. In this ever shrinking world where people, products and pathogens move rapidly around the globe, collective expertise and experience will enable researchers to find answers to the infectious disease challenges confronting society. A scientific program including cutting edge science to state-of the-art practices to global infectious disease control, all presented by an international faculty.
Suggested reading: Medical Microbiology Books

March 12, 2010 Recombinant Vaccines - Right Molecule, Right Place, Right Time?
Welwyn Garden City, UK Further information
Huge technological advances have been made recently in the genomic and post-genomic analyses of pathogens and disease. To exploit these advances for the production of successful recombinant vaccines we need strategies to select appropriate molecules and to deliver them appropriately to stimulate protective immune responses. This meeting will explore both candidate discovery and the tools for delivering vaccines effectively.
Suggested reading: Microbiology Books

March 12 - 14, 2010 The Clinical Vaccinology Course
San Diego, CA, USA Further information
Provides a comprehensive background in vaccinology for practicing clinicians.
Suggested reading: Medical Microbiology Books

March 14 - 19, 2010 New Antibacterial Discovery and Development
Galveston, TX, USA Further information
This Gordon Conference will address a critical issue regarding the availability of new antibacterial targets and developing these new targets through to useful antimicrobial agents. We will address this issue by assembling representatives of industry, academia, regulatory agencies, NIAID and, hopefully, political representatives.
Suggested reading: Bacteriology books

March 16 - 17, 2010 Invasive Fungal Infections: Host-Pathogen Interaction
Oslo, Norway Further information
ESCMID Postgraduate Education Course. Jointly organized by the ESCMID Fungal Infection Study Group (EFISG), the Antifungal Susceptibility Testing Subcommittee of th European Committee on Antimicrobial Susceptibility Testing (AFST-EUCAST) and the Nordic Society of Medical Mycology (NSMM).
Suggested reading: Mycology Books

March 17 - 18, 2010 12th Annual Superbugs and Superdrugs
London, UK Further information
Organized by SMI. Keynote address from Professor Peter Hawkey, Professor of Public Health Bacteriology, University of Birmingham and Health Protection Agency.
Suggested reading: Microbiology Books

March 21 - 26, 2010 Biology of Acute Respiratory Infection
Ventura, CA, USA Further information
Gordon Research Conference
Suggested reading: Microbiology books

March 21 - 26, 2010 HIV Vaccines
Banff, Canada Further information
Since a HIV vaccine is proving to be a particularly recalcitrant problem, a novel approach that facilitates a wider cross-fertilization of ideas would be very valuable and would be welcomed by the broader HIV vaccine research community. To that end, the major development proposed for the 2010 Keystone HIV Vaccine Symposium is to foster innovative ideas and new collaborations with immunology and vaccinology as it pertains to other viral diseases. Specifically, we propose that a new Joint Symposium of HIV Vaccines in conjunction with Viral Immunity be convened. This Joint Symposium would retain the valuable format that includes joint and separate sessions covering general and specific principles.
Suggested reading: AIDS Vaccine Development: Challenges and Opportunities

March 21 - 26, 2010 Viral Immunity
Banff, Canada Further information
The most exciting recent advances in viral immunity include the increased understanding of the role of innate immune mechanisms, interaction between innate and adaptive immunity, pathogen manipulation of host responses, and activation of immune responses and generation of immune memory. Despite these advances, basic mechanisms of anti-viral immunity are poorly characterized particularly for chronic infections. Efforts are also required to exploit recent research advances to improve vaccine design and therapeutic intervention. This meeting will include both innate and adaptive immunity and juxtapose animal models with human studies as it attempts to foster collaborative efforts between attending viral immunologists and the HIV vaccine researchers in the joint meeting. Expert talks in plenary sessions will encompass the latest in critical areas of viral immunity. Workshops and additional presentations will cover provocative and cutting-edge results from attendees. The meeting objective is to accelerate progress in understanding and manipulating anti-viral immunity to improve human health.
Suggested reading: Virology Books

March 22 - 24, 2010 Systems Biology of Microorganisms
Paris, France Further information
The current state-of-the-art in systems biology of microorganisms and the future developments and promises.
Suggested reading: Microbiology Books

March 22 - 26, 2010 10th ASM Conference on Candida and Candidiasis
Miami, FL, USA Further information
Candida is the major fungal pathogen of humans, causing infections that range from oral and vaginal candidiasis to life-threatening candidemia and invasive disease. The Candida field focuses on a broad spectrum of subjects that relate to epidemiology, drug resistance, infection, host response, and therapeutics.
Suggested reading: Candida: Comparative and Functional Genomics

March 22 - 26, 2010 2nd ASM Conference on Dimorphic Fungal Pathogens
Miami, FL, USA Further information
Session Topics on: Regulation of morphogenesis; Pathogenesis and virulence strategies; Host response to infection; Clinical diagnosis and treatment; Functional genomics and proteomics; Sequence workshop/community tool-building; Fungal evolution and selection. Of special note is the "Sequence workshop/commuity tool-building session" which will be a hands-on practical workshop where participants will be introduced to the sequenced genomes of all the dimorphic fungal pathogens as generated by the Broad Institute.
Suggested reading: Pathogenic Fungi: Insights in Molecular Biology

March 22 - 27, 2010 Role of Anaerobic Bacteria in Infections: diagnostics, Antibiotic Resistance, New Therapeutic Options
Groningen, The Netherlands Further information
ESCMID Postgraduate Technical Workshop. Jointly organized by the ESCMID Study Group for Antimicrobial Resistance in Anaerobic Bacteria (ESGARAB) and the ESCMID Study Group for Clostridium difficile (ESGCD).
Suggested reading: Bacteriology books

March 24 - 26, 2010 ISHEID 2010 - International Symposium on HIV and Emerging Infectious Diseases
Marseille, France Further information
Sessions on HIV and infectious diseases.
Suggested reading: Virology Books

March 28 - 31, 2010 3rd Joint Conference of the German Society for Hygiene and Microbiology (DGHM) and the Association for General and Applied Microbiology (VAAM)
Hannover, Germany Further information
Topics include: Antimicrobial compounds; Functional Genomics; Gene Regulation; Host Microbe Interaction; Infection and Cancer; Innate Immunity; Metabolism; MRSA; Tuberculosis
Suggested reading: Microbiology Books

March 29 - April 1, 2010 SGM Spring 2010 Meeting. Systems, Mechanisms And Micro-Organisms
Edinburgh, UK Further information
Main Theme: Systems, Mechanisms And Micro-Organisms. Scientific sessions, Posters, Exhibition, Drinks receptions, Buffet lunch. The Gala Dinner will be at the Dynamic Earth, Holyrood Road, Edinburgh EH8 8AS
Suggested reading: Microbiology Books

April 2010


April 7 - 11, 2010 Fourth European Congress Of Virology
Lake Como, Italy Further information
The Eurovirology Congresses, renamed European Virology Congresses, were initiated in 2000 to bring together young and senior investigators from all Countries of Europe and from all branches of Virology. The aim was to strengthen Virology in Europe, by providing a platform for basic, medical, clinical, veterinary, and plant Virology.
Suggested reading: Virology Books

April 8 - 17, 2010 Advanced optical microscopy 2010
Plymouth, UK Further information
EMBO Practical Course
Suggested reading: Microbiology Books

April 10 - 13, 2010 20th ECCMID
Vienna, Austria Further information
The annual congress of ESCMID, the European Congress of Clinical Microbiology and Infectious Diseases. Over 6500 participants attend.
Suggested reading: Medical Microbiology Books

April 11 - 16, 2010 Malaria: New Approaches to Understanding Host-Parasite Interactions
Copper Mountain, CO, USA Further information
Malaria has entered a new era—a partially effective vaccine may be licensed in the not too distant future, and the genomes of host, parasite and vector are now widely available. Major advances have been made in understanding basic parasite cell biology and fundamental immunology, using rapidly evolving molecular genetic technologies for both host and parasite. Systems biology approaches also offer a new paradigm for interrogating complex host responses to a complex pathogen. Future progress will require greater integration of these technologies to elucidate parasite cell biology, host-parasite interactions, and the specific mechanisms that confer protection in our model systems and in nature. This symposium will bring together these new fields to examine those aspects of host and Plasmodium biology important for understanding immunity and pathogenesis.
Suggested reading: Parasitology Booksy Books

April 11 - 16, 2010 Molecular Targets for Control of Vector-Borne Diseases: Bridging Lab and Field Research
Copper Mountain, CO, USA Further information
Vigorous research since the completion of the Anopheles gambiae genome sequence has established the malaria mosquito as a model organism for host-pathogen biology. However, the translation of this growing post-genomic knowledge base into new vector-targeted malaria control strategies is a distinct challenge that now leads laboratory-based molecular researchers to confront the complexity and heterogeneity of the natural malaria transmission system. Simultaneously, a body of field-based vector researchers has been developing new ways to utilize existing vector control tools such as bednets and insecticides that, if consistently implemented, can yield impressive outcomes. Lab and field based practitioners attend different meetings and rarely engage in direct dialog. This conference will examine the tension between the development of new practical malaria control tools, including genomic ones, and the advantages of more fully exploiting existing tools. It is hoped that the scientific discussion will help influence individual and programmatic research priorities.
Suggested reading: Borrelia: Molecular Biology, Host Interaction and Pathogenesis

April 15 - 16, 2010 SGM Irish Division
Galway, Ireland Further information
New insights in molecular microbiology through the manipulation of protein structure and function. Sessions include: Insights into microbial pathogenesis; Extending the frontiers of expression systems; Environmental microbiology: monitoring and exploitation
Suggested reading: Environmental Microbiology

April 16, 2010 SFAM Society for Applied Microbiology Spring Meeting 2010
Stratford upon Avon, UK Further information
Society for Applied Microbiology (SFAM) 2010 spring meeting focusing on Salmonella, E coli O157, Cryptosporidia, Campylobacter, Clostridium, gastrointestinal infections
Suggested reading: Microbiology Books

April 18 - 20, 2010 46th Annual Meeting of British Society for Medical Mycology (BSMM)
Exeter, UK Further information
The meeting generally attracts 80-120 delegates and covers topics from many areas of Medical Mycology. A range of international experts are contributing to this year's meeting, including a Special Retirement lecture from Professor Frank Odds (Aberdeen University) and the President's lecture from Professor Joe Heitman (Duke University).
Suggested reading: Mycology Books

April 19 - 22, 2010 32nd Symposium on Biotechnology for Fuels And Chemicals
Clearwater, FL, USA Further information
Topics related to the building of the new biomass fuels and chemicals industry. There is a session on development of new biomass sources, and a session on production and logistics to get feedstock to the biorefinery. Advances in pretreatment, microbial conversion and enzyme advances will be presented in two sessions each divided between fundamental and more applied aspects. Developments in bioprocessing and separations will be discussed in one session.
Suggested reading: Microbiology Books

April 19 - 23, 2010 Molecular Typing Methods for Bacterial Pathogens
Zagreb, Croatia Further information
ESCMID Postgraduate Technical Workshop
Suggested reading: Bacteriology books

April 24 - 28, 2010 2nd ASM Conference on Mobile DNA
Montreal, Canada Further information
Suggested reading: Molecular Biology Books

April 26 - 28, 2010 13th Annual Conference on Vaccine Research
Baltimore, MD, USA Further information
The latest vaccine-related scientific data, results, and issues via symposia and panel discussions by expert faculty and through oral and poster sessions.
Suggested reading: Microbiology Books

May 2010


May 5 - 7, 2010 RNAi and miRNA World Congress
Boston, MA, USA Further information
Topics include: Target Discovery and Validation, Transfection, in vivo RNAi, siRNA library screens, microRNAs in, Disease Biology, Stem Cell Biology, Diagnostics, Virology, Biogenesis, Development,
Suggested reading: RNA Interference and Viruses: Current Innovations and Future Trends

May 5 - 8, 2010 ISOPOL XVII (International Symposium on Problems of Listeriosis)
Porto, Portugal Further information
ISOPOL XVII will bring together specialists from a wide range of scientific disciplines from all over the world (from Vets, Medics, Bioscientists to Public-Health and Food Industry specialists, from junior researchers to world-leaders in their fields) to discuss the most important and up to date issues concerning Listeria and Listeriosis.
Suggested reading: Foodborne Pathogens: Microbiology and Molecular Biology

May 6 - 7, 2010 Brucellosis: Epidemiological, Microbiological, Clinical and Therapeutic Aspects
Kusadasi, Turkey Further information
Organized by the Turkish Society of Clinical Microbiology and Infectious Diseases (KLIMIK)
Suggested reading: Medical Microbiology Books

May 20 - 23, 2010 ASM 17th Annual Conference for Undergraduate Educators ASMCUE
San Diego, CA, USA Further information
ASMCUE is an interactive four-day conference on scientific updates and effective teaching strategies. Each year, the conference attracts approximately 300 microbiology and biology educators.

May 23 - 27, 2010 110th General Meeting of the American Society for Microbiology
San Diego, USA Further information
The scientific program will feature nearly 300 individual colloquia, symposia, roundtable discussions, award lectures, and poster sessions. The 27 Division Chairs and the General Meeting Program Committee have devoted their energies to creating a well-rounded program.
Suggested reading: Microbiology Books

May 26 - 30, 2010 Banff Conference on Infectious Diseases 2010
Banff, Canada Further information
15th biennial meeting. An international meeting where renowned experts present their most up to date research results on diverse aspects of Infectious Diseases. Plenary lecture by Dr. John Mekalanos of Harvard University.
Suggested reading: Medical microbiology books

May 30 - June 4, 2010 Antiviral applications of RNA interference
Sant Feliu de Guixols, Spain Further information
ESF-EMBO Symposia
Suggested reading: RNA Interference and Viruses: Current Innovations and Future Trends

June 2010


June 1 - 4, 2010 Emerging themes in infection biology
Nice, France Further information
EMBO Workshop
Suggested reading: Bacteriology Books

June 1 - 4, 2010 3rd International Symposium on Propionibacteria and Bifidobacteria: Dairy and Probiotic Applications
Oviedo, Spain Further information
This symposium aims to present the current advances in dairy propionibacteria and bifidobacteria, considering the important role that they play in dairy industrial applications as well as in human health.
Suggested reading: Lactobacillus

June 6 - 10, 2010 14th International Conference on the Cell and Molecular Biology of Chlamydomonas
Norton, MA, USA Further information
The Chlamydomonas research community meets every two years. These meetings usually bring together approximately 200 scientists for 5 days of presentations and discussion. Newcomers are always welcome.
Suggested reading: Microbiology Books

June 7 - 11, 2010 Postgraduate Workshop in Clinical Parasitology
Amsterdam, The Netherlands Further information
Postgraduate Workshop in Clinical Parasitology and ESCMID Postgraduate Technical Workshop
Suggested reading: Parasitology Books

June 8 - 11, 2010 2nd ASM Conference on Mobile DNA
Quebec, Canada Further information
This meeting will bring together researchers interested in all aspects of specialized recombination, from the biological to the structural and mechanistic. Research probing transposition in diverse organisms, including eubacteria, archaea, protists, plants, and animals, will be presented to showcase diversity of transposable elements and their genomic consequences and to underscore unifying principles.
Suggested reading: Molecular Biology Books

June 8 - 11, 2010 2nd ASM Conference on Antimicrobial Resistance in Zoonootic Bacteria and Foodborne Pathogens
Toronto, Canada Further information
Suggested reading: Foodborne Pathogens: Microbiology and Molecular Biology

June 11 - 15, 2010 Genomic approaches to interactions between plant viruses, their hosts and their vectors
Fenestrelle, Italy Further information
EMBO Workshops
Suggested reading: Virology Books

June 12 - 16, 2010 Genomic approaches to interactions between plant viruses, their hosts and their vectors
Fenestrelle, Italy Further information
EMBO Workshop
Suggested reading: Plant Pathogenic Microorganisms

June 13 - 18, 2010 Cellular and Molecular Fungal Biology
Holderness, NH, USA Further information
The Cellular and Molecular Fungal Biology Conference provides a forum for presentation of the latest advances in fungal research with an emphasis on filamentous fungi. This open-registration scientific meeting brings together the leading scientists from academia, government and industry to discuss current research results and future directions
Suggested reading: Fungal Biology Books

June 14 - 17, 2010 60th CSM Annual Conference of the Canadian Society of Microbiologists
Hamilton, ON, Canada Further information
The 2010 Annual Conference of the Canadian Society of Microbiologists will be held in McMaster University, organized under the direction of the Chairs of the local organizing committee, Marie Elliot and Turlough Finan
Suggested reading: Microbiology

June 15 - 17, 2010 International Probiotic Conference - IPC 2010
Kosice, Slovakia Further information
International Scientific Conference on Probiotics and Prebiotics. The scientific programme will focus on current advances in the research, production and use of probiotics and prebiotics with particular focus on their role in maintaining health and preventing diseases.
Suggested reading: Lactobacillus

June 16 - 18, 2010 Viruses and innate immunity
Dublin, Ireland Further information
EMBO Workshop
Suggested reading: Virology Books

June 19 - 24, 2010 Gene transcription in yeast
San Feliu de Guixols, Spain Further information
EMBO Conference Series. Gene transcription in yeast from mechanisms to functional genomics
Suggested reading: Mycology Books

June 20 - 25, 2010 8th Workshop "Professor V.J. Benedi" Mechanisms of Antimicrobial Resistance - a Practical Approach
Palma de Mallorca, Spain Further information
ESCMID Postgraduate Technical Workshop
Suggested reading: Microbiology Books

June 20 - July 2, 2010 Virology Masterclass
Adelaide, Australia Further information
The 3rd Australasian Virology MasterClass is a unique post graduate course in Medical Virology offered by specialist practitioners working in the discipline. This intense two week course has been established to provide up to date and comprehensive information relevant to modern diagnostic, molecular and clinical virology. The 2006 and 2007 Virology MasterClasses attracted participants from Australia, New Zealand, Hong Kong, Singapore and Brunei. Highly acclaimed and previously oversubscribed, the course will offered again in 2010.
Suggested reading: Virology Books

June 21 - 25, 2010 14th International Negative Strand Virus Meeting
Bruges, Belgium Further information
Recent developments in basic research on negative strand viruses, including progress in high resolution structure determination, the control of negative strand viral RNA synthesis, and the cellular innate response to negative strand virus infection etc.
Suggested reading: Current virology publications

June 21 - 25, 2010 Viruses of Microbes
Paris, France Further information
This First International Congress on Virus of Microbes marks a new era in viral research, which has begun with the recognition that viruses are the predominant component of the biosphere numerically, with a considerable impact on the planet's ecology, and represent the greatest genetic resource in the biosphere, significantly affecting biosystem's evolution. At the meeting will be highlighted global aspects of problems concerning the diversity, ecology, and environmental impact of viruses infecting Bacteria, Archaea and microbial Eukaryotes. Actively will be discussed also problems of the origin and nature of viruses, and their role in early life evolution. Particular attention will also be given to technological and medical applications of microbial viruses, including their exploitation in "phage display" studies, their potential in developing new advanced materials for nanotechnology, and their medical application.
Suggested reading: Virology Books

June 22 - 25, 2010 Gut Microbiology Conference: New Insights into gut microbial ecosystems
Aberdeen, UK Further information
The aim of the conference is to promote understanding of the complex microbial ecosystems that are present in the digestive tract of man and animals, and their interactiosn with the host.
Suggested reading: Lactobacillus Molecular Biology: From Genomics to Probiotics

June 24 - 25, 2010 The 69th annual congress of the Swiss Society Microbiology (SSM)
Zurich, Switzerland Further information
Approx 350 microbiologists are expected to attend the Swiss Society for Microbiology (SSM) annual meeting co-chaired by Leo Eberl (UniZH) and Martin Lössner (ETHZ)
Suggested reading: Microbiology

June 27 - 30, 2010 World Congress on Industrial Biotechnology and Bioprocessing
Washington, D.C., USA Further information
Held annually by the Biotechnology Industry Organization (BIO), the World Congress on Industrial Biotechnology and Bioprocessing brings together scientists, industry and government leaders, and academia from around the globe to exchange ideas about the growing biotechnology industry. Includes presentations on topics including biotechnology for climate change, cellulosic biofuels, renewable chemical platforms, energy from algae, specialty chemicals, food ingredients and more. Features plenary sessions, international networking opportunities, and business partnering meetings.
Suggested reading: Molecular Biology Books

June 27 - July 2, 2010 Bacterial Cell Surfaces
New London, NH, USA Further information
The 2010 Gordon Conference on Bacterial Cell Surfaces will feature novel and exciting research results on the molecular and cellular aspects of the structure, function, and biogenesis of bacterial envelopes and surfaces. The Conference will cover a wide range of topics, including envelope biogenesis, protein localization and secretion, nutrient transport, extracellular matrices and surface polymers, signal sensing and transduction, cell envelope stress response, microbial communities and antibiotics, and cell morphogenesis.
Suggested reading: Bacteriology books

June 27 - July 2, 2010 Biology of Host-Parasite Interactions
Newport, RI, USA Further information
The 2010 GRC conference on Biology of Host-Parasite Interactions will present the latest findings on the biology of protozoan parasites and their vectors, with special emphasis on human and animal diseases such as malaria, toxoplasmosis, African and American trypanosomiasis, leishmaniasis, trichomoniasis, giardiasis and entamoebiasis.
Suggested reading: Parasitology Booksy Books

June 28 - July 1, 2010 11th International Symposium on Genetics of Industrial Microorganisms GIM
Melbourne, Australia Further information
GIM is a special meeting that occurs once every four years and this will be the first time GIM has been held in Australia. Genetics and physiology of industrially important microorganisms; Sustainability and global resource management using microbial genetic resources; Omics of environmental technologies; Microbial processes for food and beverage industry; Microbial genome structure and evolution; Search and biodiscovery of new therapeutic agents; Viral genetics; New and alternative therapies
Suggested reading: Bacteriology books

July 2010


July 3 - 8, 2010 26th International Papillomavirus Conference and Workshops
Montreal, Canada Further information
HPV 2010. Twenty-Sixth Annual International Papillomavirus Conference and Clinical Workshop
Suggested reading: Papillomavirus Research: From Natural History To Vaccines and Beyond

July 4 - 8, 2010 ASM Annual Scientific Meeting and Exhibition
Sydney, Australia Further information
Topics include: Antimicrobial Resistance, Emerging Viruses, Genomics, Systems Biology, Cell Signaling, Symbiosis, Virus - Cell Interactions, Soil Microbiology, Molecular Mycology, Gut Microbiology, and much more.
Suggested reading: Bacteriology Books

July 4 - 9, 2010 Marine Microbes: From Genes To Global Cycles
Tilton, NH, USA Further information
Marine microbes include representatives from all three kingdoms of life and collectively carry out virtually all forms of metabolisms found on the planet. Because of this metabolic and genetic diversity, these microbes mediate many of the reactions making up global biogeochemical cycles which govern the flow of energy and material in the biosphere. The goal of this conference is to bring together approaches and concepts from studies of microbial evolution, genomics, ecology, and oceanography in order to gain new insights into marine microbes and their biogeochemical functions.
Suggested reading: Microbiology Books

July 5 - 8, 2010 Society for Applied Microbiology Summer Conference
Brighton, UK Further information
Applied microbiology with sessions on: Biofilms, Listeria, Bacteriophages. Including the Lewis B Perry Memorial Lecture
Suggested reading: Microbiology Books

July 7 - 10, 2010 Anaerobe 2010: 10th Biennial Congress of the Anaerobe Society of the Americas
Philadelphia, PA, USA Further information
This meetings brings together researchers and clinicians to discuss all aspects of anaerobic bacteriology.
Suggested reading: Bacteriology Books

July 10 - 11, 2010 Microbial Toxins and Pathogenicity Gordon Research Seminar
Waterville Valley, NH, USA Further information
The Gordon Research Seminar on Microbial Toxins and Pathogenicity is a unique forum for graduate students, post-docs, and other scientists with comparable levels of experience and education to present and exchange new data and cutting edge ideas.
Suggested reading: Microbial Toxins: Current Research and Future Trends

July 11 - 16, 2010 18th International Congress of the IOM
Terme, Italy Further information
A diverse and active international scientific community of researchers, diagnosticians and students present and discuss topics covering all aspects of mycoplasmology. This includes: mycoplasma, phytoplasma, ureaplasma, acholeplasma, haemoplasma and spiroplasma species; their hosts; research on these organisms; their disease characteristics; their effects; transmission; control; as well as diagnostic and research methods.
Suggested reading: Microbiology Books

July 11 - 16, 2010 Microbial Toxins and Pathogenicity
Waterville Valley, NH, USA Further information
The 2010 Gordon Research Conference on Microbial Toxins and Pathogenicity is an outstanding forum to acquire cutting-edge knowledge on microbial pathogenesis. The organization of the conference includes seminars on the basic mechanisms of microbial pathogenesis, from primarily bacterial systems, with seminar sessions on toxin biochemistry and biogenesis, molecular and cellular pathogenesis, and infection and immunity.
Suggested reading: Microbial Toxins: Current Research and Future Trends

July 17 - 21, 2010 American Society For Virology 29th Annual Scientific Meeting
Bozeman, MT, USA Further information
The 2010 ASV scientific program will include symposia and concurrent sessions on multiple aspects of virology.
Suggested reading: Virology books

July 18 - 23, 2010 AIDS Congress
Vienna, Austria Further information
AIDS 2010 will mark an important milestone: the deadline by which world leaders have committed to ensuring universal access to HIV prevention, treatment, care and support. The conference will be an opportunity to evaluate progress to date and to identify what must be done, both individually and collectively, to achieve this critical goal. With an estimated 25,000 participants and 2,500 media in attendance
Suggested reading: Retroviruses: Molecular Biology, Genomics and Pathogenesis

July 18 - 23, 2010 Microbial Stress Response
South Hadley, MA, USA Further information
Gordon Research Conference

July 30 - August 2, 2010 3rd ASM Conference on Enterococci
Portland, USA Further information
Suggested reading: Bacteriology Books

August 2010


August 1 - 4, 2010 IAFP 2010
Anaheim, CA, USA Further information
International Association for Food Protection (IAFP) conference
Suggested reading: Foodborne Pathogens: Microbiology and Molecular Biology

August 1 - 5, 2010 SIM 60th Annual Meeting and Exhibition (Society For Industrial Microbiology)
San Francisco, CA, USA Further information
Annual meeting of the Society For Industrial Microbiology
Suggested reading: Microbiology Books

August 1 - 6, 2010 IMC9: The Biology of Fungi
Edinburgh, UK Further information
Fungal biology has never been as important as it is today and this is undoubtedly the most exciting time to be studying the subject. The International Mycological Congress represents the greatest scientific forum to provide an up-to-date perspective of mycology in all its guises. The 9th International Mycological Congress (IMC9: the Biology of Fungi) will be hosted by the British Mycological Society in 2010 in Edinburgh, Scotland.
Suggested reading: Fungal Biology Books

August 1 - 6, 2010 Molecular Basis of Microbial One-Carbon Metabolism
Lewiston, ME, USA Further information
Gordon Research Conference
Suggested reading: Molecular Microbiology

August 8 - 13, 2010 Plant and Microbial Cytoskeleton
Andover, NH, USA Further information
The Gordon Conference on Plant and Microbial Cytoskeleton focuses on recent advances in the study of cytoskeletal biology and mechanism in plants, fungal organisms, bacteria, and other microbes.
Suggested reading: Microbiology Books

August 14 - 18, 2010 9th International Symposium on the Microbiology of Aerial Plant Surfaces
Corvallis, OR, USA Further information
The meeting seeks to bring together researchers from the plant and the microbial side and will include the areas of aerobiology, anatomy, bacteriology, biochemistry, biological control, micro-meteorology, mycology, plant physiology, plant pathology, and molecular biology in order to further our understanding the ecology of foliar plant surfaces in both aquatic and terrestrial environments.
Suggested reading: Microbiology Books

August 22 - 27, 2010 13th International Symposium on Microbial Ecology ISME13
Seattle, WA Further information
ISME-13 STEWARDS OF A CHANGING PLANET. International symposium organized by the International Society for Microbial Ecology. The 13th International Society for Microbial Ecology Conference will be in Seattle, USA from August 22 - 27, 2010. There is a vibrant scientific program planned with plenary presenters; Penny Chisholm, Jeffrey Gordon, Ove Hoegh-Guldberg, Ian Sanders, Christa Schleper, and Warwick Vincent.
Suggested reading: Environmental Molecular Microbiology

August 26 - September 4, 2010 Viral vectors in gene therapy: applications and novel production methods
Kuopio, Finland Further information
EMBO Practical Courses
Suggested reading: Virology Books

August 31 - September 10, 2010 Host-microbes interactions
Spetses, Greece Further information
EMBO/FEBS Lecture Course
Suggested reading: Microbiology Books

September 2010


September 1 - 3, 2010 8th International Symposium on the Biology of Acinetobacter
Rome, Italy Further information
The aim of these meetings is to provide an informal international forum in which to discuss all aspects of the genus Acinetobacter. In particular, it is hoped to stimulate discussion and collaboration between medical and non-medical microbiologists, all of whom deal with this ubiquitous group of organisms in the course of their working lives.
Suggested reading: Acinetobacter Molecular Biology

September 1 - 3, 2010 Biofilms4 International Conference
Winchester, UK Further information
The fourth International Biofilms Conference
Suggested reading: Microbiology Books

September 2 - 3, 2010 SGM Irish Division
Maynooth, Ireland Further information
Insect-mediated microbial diseases of human and animals: Current problems and Future threats. Insect-borne microbial pathogens are responsible for large numbers of deaths of animals and humans each year. Malaria, transmitted by Mosquitos (Anopholes), is responsible for up to 1 million human deaths per annum while Trypanosomiasis, which is transmitted by the Tsetse fly, affects livestock in sub-Saharan Africa, South Asia and South America and is responsible for the loss of large numbers of animals and the perpetuation of the poverty associated with many of these regions.
Suggested reading: Medical Microbiology books

September 2 - 4, 2010 An Infection That Will Never Be Out of Date: Influenza
Istanbul, Turkey Further information
ESCMID Postgraduate Education Course. Jointly organized by the Turkish Microbiology Society and ESCMID.
Suggested reading: Influenza Molecular Biology

September 3 - 7, 2010 Options for the Control of Influenza VII
Hong Kong, Further information
Largest forum solely focused on the prevention, control, and treatment of influenza. Most recent advances in the science of influenza
Suggested reading: Influenza Molecular Biology

September 5 - 7, 2010 Advances in Plant Virology
Wageningen, The Netherlands Further information
A conference organized by Association of Applied Biologists and the Dutch Society of Plant Virologists.
Suggested reading: Virology Books

September 6 - 9, 2010 SGM Autumn 2010 Meeting.
Nottingham, UK Further information
Scientific sessions, posters, exhibition
Suggested reading: Microbiology Books

September 6 - 9, 2010 14th International Symposium on Staphylococci and Staphylococcal Infections (ISSSI)
Bath, UK Further information
The programme will cover a diverse range of subjects on staphylococcal research including disease management, pathogenesis, immune evasion, persistence, population biology, evolution and regulation. The plenary and symposium sessions will be presented by the world\'s leading experts in each of these fields.
Suggested reading: Staphylococcus: Molecular Genetics

September 6 - 10, 2010 9th European Nitrogen Fixation Conference
Geneva, Switzerland Further information
Topics include: Applied aspects of biological nitrogen fixation; Evolution and diversity of diazotrophs and hosts; Genomics and post-genomics of diazotrophs and hosts; Interactions of proteobacteria with legumes; Interactions of diazotrophs with non-legume hosts; Novel tools and technologies to study diazotrophy; Physiology of free-living and symbiotic diazotrophs; Regulation of nitrogen fixation; Structure and function of nitrogenase.
Suggested reading: Microbiology Books

September 6 - 10, 2010 14th Workshop of the International Study Group for Systems Biology 2010
Vladimir, Russia Further information
The International Study Group for Systems Biology is a collective of international researchers interested in advancing the biological sciences through exploring the interplay between theory and experiment. The general theme is theoretical approaches to understanding the behaviour of cell systems, particularly transport, metabolism and signal transduction.
Suggested reading: Molecular Biology Books

September 6 - 10, 2010 XXXIII International Congress of the Society for Microbial Ecology and Disease
Cruiseship Aegean Pearl, Greece Further information
1st Day, Medical Microbial Ecology; 2nd Day, Dental Microbial Ecology; 3rd Day, Nutrition, Probiotics, Food and Water Microbial Ecology Health Related 4th Day, Environmental Microbial Ecology. The cruise programme includes some of the most well known Greek Islands such as Cosmopolitan Myconos, Rhodes, Patmos, Crete, the fascinating island of Santorini and Ephesus and Kusadasi in Turkey.
Suggested reading: Environmental Molecular Microbiology

September 8 - 10, 2010 Meningitis
Izmir, Turkey Further information
ESCMID Postgraduate Education Course. Jointly organized by the ESCMID Meningitis Study Group (EMESG), the Infectious Diseases and Clinical Microbiology Specialty Society of Turkey (EKMUD) and the Turkish Society of Hospital Infection and Control.
Suggested reading: Neisseria: Molecular Mechanisms of Pathogenesis

September 12 - 15, 2010 50th ICAAC Interscience Conference on Antimicrobial Agents and Chemotherapy
Boston, USA Further information

September 12 - 15, 2010 Interscience Conference on Antimicrobial Agents and Chemotherapy ICAAC
Boston, MA, USA Further information
More than 10,000 physicians, researchers and other healthcare professionals from around the globe gather each year at ICAAC
Suggested reading: Microbiology Books

September 12 - 16, 2010 8th INTERNATIONAL CONGRESS ON EXTREMOPHILES
Azores, Portugal Further information
EXTREMOPHILES 2010
An international forum to appreciate the current state of the art of Extremophiles and to discuss how science in this field can contribute to finding solutions to the challenges we face in the future.
Suggested reading: Archaea: New Models for Prokaryotic Biology

September 14 - 15, 2010 3rd Symposium on Potato Cyst Nematodes
Newport, UK Further information
Association of Applied Biologists: Nematology Group
Suggested reading: Anaerobic Parasitic Protozoa: Genomics and Molecular Biology

September 14 - 15, 2010 Advances in qPCR
Dublin, Ireland Further information
Topics include: qPCR in Diagnostics, Detection of Tumour Cells, microRNA/siRNA Applications, High Resolution Melt, Chip / location analysis, Single Cell qPCR, BioStatistics and Bioinformatics, Expression Profiling
Suggested reading: Real-Time PCR: Current Technology and Applications

September 14 - 15, 2010 RNAi and miRNA Europe
Dublin, Ireland Further information
Topics include: Target Discovery and Validation, Transfection, in vivo RNAi, siRNA library screens, microRNAs in, Disease Biology, Stem Cell Biology, Diagnostics, Virology, Biogenesis, Development,
Suggested reading: RNA Interference and Viruses: Current Innovations and Future Trends

September 18, 2010 Antimicrobial Chemotherapy in Daily Practice
Barcelona, Spain Further information
GRACE Postgraduate Education Course This course is organized in collaboration with the European Respiratory Society (ERS) at the ERS Annual Meeting
Suggested reading: Microbiology Books

September 24 - 26, 2010 MICROBE 2010
Sheffield, UK Further information
Medical microbiology conference, with comprehensive lecture programme and large trade exhibition. Microbe symposia are held every 2 years.
Suggested reading: Microbiology Books

September 26 - 30, 2010 2nd ASMET - The ASM Emerging Technologies Conference
Cancun, Mexico Further information
Suggested reading: Molecular Biology Books

September 27 - 30, 2010 Antimicrobial Susceptibility Testing and Surveillance: from Laboratory to Clinic - the EUCAST and ESGARS Perspective
Madrid, Spain Further information
ESCMID Postgraduate Education Course
Suggested reading: Microbiology Books

September 28 - October 1, 2010 First European Student Conference on Microbial Communication
Jena, Germany Further information
MICOM 2010. The conference is a gathering of Ph.D. students and experienced researchers from all over the world who will actively discuss and exchange ideas on the different aspects of microbial communication. Topics include the interaction of microorganisms with other microorganisms, higher organisms, human hosts, and their environment; and also the use of physical sciences and bioinformatics to study them. It is a great opportunity to learn about the recent state-of-the-art approaches in the investigation of microbial interactions and to meet scientists working in the same field. The program consists of scientific talks, inspiring workshops in small groups (Meet the scientist) given by leading scientists in the field of microbial communication as well as social and cultural events.
Suggested reading: Environmental Molecular Microbiology

September 29 - October 3, 2010 Experimental approaches to evolution and ecology using yeast
Heidelberg, Germany Further information
EMBO Conference Series
Suggested reading: Books on Yeast and Mycology

October 2010


October 6 - 9, 2010 Prato Conference on the Pathogenesis of Bacterial Diseases of Animals
Prato, Italy Further information
Established by the ARC (Australian Research Council) Centre of Excellence in Structural and Functional Microbial Genomics to bring together researchers working in areas relevant to the mechanisms by which bacteria cause disease in animals.
Suggested reading: Microbiology Books

October 6 - 9, 2010 11th annual meeting of the International Endotoxin and Innate Immunity Society
Vancouver, Canada Further information
The joint meeting of the International Endotoxin and Innate Immunity Society and the Society of Leukocyte Biology. This biannual meeting covers all aspects of endotoxin biology and innate immunity. The theme is The Three Rs of Immunity: Recognition, Response, Resolution.
Suggested reading: Microbial Toxins: Current Research and Future Trends

October 9 - 14, 2010 Cell biology meets microbiology
Krakow, Poland Further information
EMBO Conference Series
Suggested reading: Microbiology Books

October 21 - 22, 2010 CRISPR Mechanisms and Applications
Wageningen, The Netherlands Further information
The recently discovered CRISPR defense system protects bacteria and archaea against mobile genetic elements. This two-day CRISPR meeting focusses on the CRISPR mechanism of action and applications, and aims at discussing the latest developments in this exciting research field.
Suggested reading: Microbiology Books

October 25 - 29, 2010 3rd ASM Conference on Beneficial Microbes
Miami, USA Further information
Suggested reading: Probiotics Books

October 28 - 29, 2010 Molecular Diagnostics World Congress
San Diego, CA, USA Further information
Topics include: Molecular Diagnostics and Biomarkers, PGx and Personalized Medicine, Emerging Technologies, Clinical Applications of Molecular Diagnostics, Commercial and Regulatory Perspectives
Suggested reading: Real-Time PCR: Current Technology and Applications

November 2010


November 2 - 5, 2010 Intracellular Bacteria: from Biology to Clinic
Sousse, Tunisia Further information
ESCMID Postgraduate Education Course
Suggested reading: Bacteriology books

November 16 - 19, 2010 Bacterial Cell Biology conference
Puerto Morelos, Mexico Further information
Chaired by Jeff Errington (University of Newcastle)
Suggested reading: Microbiology Books

November 30 - December 3, 2010 VIth World Melioidosis Congress
Townsville, Queensland, Australia Further information
6th World Melioidosis Congress
Suggested reading: Burkholderia: Molecular Microbiology and Genomics

November 30 - December 3, 2010 NZ Microbiological Society and NZ Society for Biochemistry and Molecular Biology joint meeting
Auckland, New Zealand Further information
This is a multidisciplinary conference generally attracting 200-300 delegates. Most participants are NZ-based, although the conference also has a range of renowned international plenary speakers, encompassing diverse fields such as medical microbiology, wine science, food microbiology, industrial microbiology, microbial ecology, systems biology and molecular evolution.
Suggested reading: Molecular Microbiology Books


Microbiology Conferences 2011


Any conference missing from this list? Please send details

April 2011


April 11 - 14, 2011 SGM Spring 2011 Meeting
Harrogate, UK Further information
The SGM Spring Meeting will be the largest gathering of microbiologists in the UK in 2011. Delegates from all fields and at all stages of their career will find much to interest them.
Suggested reading: Microbiology Books

June 2011


June 26 - 30, 2011 4th Congress of European Microbiologists FEMS
Geneva, Switzerland Further information
Organized by the Federation of European Microbiological Societies (FEMS)
Suggested reading: Microbiology Books

July 2011


July 16 - 20, 2011 American Society For Virology 30th Annual Scientific Meeting
Minneapolis, USA Further information
Annual meeting of the American Society For Virology
Suggested reading: Recommended reading in virology

September 2011


September 6 - 11, 2011 XIII International Congress of Bacteriology and Applied Microbiology
Sapporo, Japan Further information
IUMS conference. International Union of Microbiological Societies 2011
Suggested reading: Bacteriology books

September 6 - 11, 2011 XIII International Congress of Mycology
Sapporo, Japan Further information
IUMS conference. International Union of Microbiological Societies 2011
Suggested reading: Mycology Books

September 11 - 16, 2011 XV International Congress of Virology
Sapporo, Japan Further information
IUMS conference. International Union of Microbiological Societies 2011
Suggested reading: Virology Books

September 19 - 24, 2011 15th International Biodeterioration and Biodegradation Symposium (IBBS 15)
Vienna, Austria Further information
Dedicated to different topics dealing with biodeterioration and biodegradation of organic and inorganic materials including cultural heritage objects, medical devices, corrosion of metals and other applied aspects such as hydrocarbons and pollutants biodegradation and techniques applied to the study of microorganisms involved in these processes.
Suggested reading: Microbial Biodegradation

Microbiology Conference List
Any conference missing from this list? Please send details

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Diagnostic Microarray for Influenza, MChip

Rapid and accurate diagnostic methods for typing and subtyping influenza viruses are needed for improved worldwide surveillance. Although molecular-based diagnostic methods are becoming more widespread in influenza diagnosis, they generally involve amplification of the hemagglutinin (HA) and/or neuraminidase (NA) gene segments for subtyping. A low-density microarray (MChip) has been developed that allows for the identification and subtyping of influenza A viruses in approximately seven hours.

MChip is unique in that it is based solely on the matrix (M) gene segment which has enough genetic diversity for subtype analysis but sufficient genetic stability to circumvent the need for continual redesign of primers and microarray probes.

Further reading:

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Influenza Polymerase

The influenza virus RNA-dependent RNA polymerase is a heterotrimeric complex (PA, PB1 and PB2) with multiple enzymatic activities for catalyzing viral RNA transcription and replication. Its critical roles in the influenza virus life cycle and high sequence conservation suggest it should be a major target for therapeutic intervention. However, until very recently, functional studies and drug discovery targeting the influenza polymerase have been hampered by the lack of three-dimensional structural information. The influenza polymerase holds prospects for the development of anti-influenza therapeutics.

Further reading:

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The 1918 Pandemic Influenza Virus

The pandemic influenza virus of 1918 was extremely virulent and caused significant morbidity and mortality to millions of people worldwide. The extinct virus caused severe pathology in both the upper and lower respiratory tract, resulting in fatal respiratory complications and bacterial pneumonia. The pathology associated with 1918 influenza virus infections is thought to be the result of the exposure of an immunologically naive host population to an unusually virulent virus.

Using reverse genetics, the 1918 pandemic virus has been studied in an attempt to determine which viral genes contribute to the increased virulence. Studies to date point to the role of the hemagglutinin, neuraminidase, and the polymerase basic protein 1 genes as the virulence genes responsible for the high pathogenicity seen with the 1918 influenza virus.


Further reading:

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Influenza M2 Channel

Viral ion channels have minimalist architecture. Despite their relatively simple structure, viral channels can achieve highly specific gating and selection of ions, and the particular mechanisms appear to be different from those of prokaryotes and eukaryotes. The unique structural and functional properties of viral channels make them ideal targets for antiviral therapy because the molecules that inhibit viral ion channels may not interact with human ion channels.

The M2 proton channel of influenza A virus is a model viral ion channel. This small channel, whose pore is formed by four equivalent transmembrane helices, is the target of two widely used anti-influenza A drugs, amantadine and rimantadine, both belonging to the adamantane class of compounds. However, resistance of influenza A to adamantane is now widespread. Naturally-occurring resistants mutants have been observed in as many as six different positions in the transmembrane segment of M2. How could there be so many different resistance-conferring mutations along a transmembrane helix of 25 amino acids? The recently-determined high-resolution structures of M2 in complex with adamantane allow us to begin answering this question read more ...

Further reading:

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Influenza A Virus Hemagglutinin Glycoproteins

The influenza A virus hemagglutinin glycoprotein (HA) is the principle mediator of viral entry into host cells. It is responsible for attachment of virions to sialic acid-containing receptors on the host cell surface, and for inducing membrane fusion between viral envelopes and cellular endosomal membranes following endocytosis. HA serves a classic example of a type I membrane glycoprotein, with a cleaved N-terminal signal sequence, a membrane anchor domain near the C-terminus, and post-translational modifications resulting from the addition of N-linked oligosaccharide side chains to the ectodomain, and acylation of cysteine residues in the cytoplasmic tail region.

HA spikes on the viral surface are also the major target for neutralizing antibodies, and as such, the antigenic properties of the HA are of fundamental significance for the design of influenza vaccines. The depth of knowledge relating to high resolution atomic structures of HA in various forms have made it a prototype for the investigation of viral glycoproteins in general.

Further reading:

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Influenza A Virus Nucleoprotein

The (-) RNA genome of the influenza A virus, eight segments in total, is encapsidated in the form of ribonucleoprotein (RNP) complexes. The nucleoprotein (NP), the major protein component of RNPs, binds along the entire length of each genomic RNA segment at a 24-nt interval, forming the double-helical RNP structures found in mature viruses. The viral polymerase, consisting of PA, PB1, and PB2 subunits, binds to the two RNA termini of the RNP.

As one of the most abundant proteins made in infected cells, influenza virus NP has essential roles in many important viral processes, including intracellular trafficking of the viral genome, viral RNA replication, viral genome packaging, and virus assembly. The recently determined crystal structures of two NP trimers show an overall fold and an external RNA binding mode that are different from rhabdovirus NP, as confirmed by a new cryo-EM reconstruction of a mini-RNP. Site-directed mutagenesis and RNA binding assays have confirmed that a positively charged groove plays an important role in NP:RNA binding. Other exciting results from recent studies include NP oligomerization, NP RNA binding, NP intracellular trafficking, NP phosphorylation, and NP-supported viral RNA replication. These new findings have led to a more detailed model for RNP structure and assembly read more ...


Further reading:

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Influenza non-structural protein 1

The non-structural protein 1 (NS1) of influenza virus is a potent antagonist of the cellular antiviral interferon (IFN) response. It is a multifunctional protein with two domains, a dsRNA binding domain (RBD) and an effector domain (ED) which interacts with various cellular proteins. Although, initially sequestration of dsRNA was considered the primary mechanism for countering IFN, subsequent studies have shown that the interactions of ED with various cellular proteins are likely involved. NS1 is shown to be a virulence determinant, especially in the highly pathogenic H5N1 viruses that are currently a threat for another influenza pandemic.

Among various influenza virus strains, NS1 is relatively well conserved with major differences occurring in the linker region and the C-terminus, where several NS1 proteins contain truncations. How these differences contribute to virulence remains unknown but these differences seem to have an effect on NS1 function that may be strain specific. In recent years, substantial progress has been made toward understanding of the structural aspects of this two-domain protein.

Further reading:

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The NS1 protein of influenza A viruses is a small (230-237-amino acid), multi-functional dimeric protein that participates in both protein-RNA and protein-protein interactions. It is comprised of two functional domains: N-terminal (amino acids 1-73) RNA-binding domain; and C-terminal (amino acids 74-230/237) effector domain. Here we focus on several of the best-characterized functional interactions of the NS1 protein.

A major role of the NS1 protein is to counter host cell antiviral responses. Thus, the RNA-binding domain binds double-stranded (ds) RNA, thereby inhibiting the dsRNA activation of the antiviral oligo A synthetase/RNase L pathway that is induced by interferon-α/β (IFN-α/β). A region of the effector domain binds the protein kinase PKR, thereby preventing its activation that would otherwise lead to the shutdown of both viral and host protein synthesis. Another region of the effector domain binds the 30 kDa subunit of the cleavage and polyadenylation specificity factor (CPSF30), a cellular protein required for the 3' end processing of all cellular pre-mRNAs.

As a consequence, the substantial amount of IFN-β pre-mRNA that is synthesized in virus-infected cells is not processed to form mature IFN-β mRNA, thereby suppressing the IFN response. The NS1 protein also has other functions that are not directly involved in countering host antiviral responses. The effector domain of the NS1 protein binds the P85β regulatory subunit of phosphoinositide 3-kinase (PI3K), resulting in the activation of PI3K and the Akt kinase, which in turn inhibits apoptosis.

The C-termini of pathogenic influenza A viruses have a PDZ-binding motif that has been implicated in pathogenicity. The NS1 protein also interacts with the cellular nuclear export protein (TAP), and may have a role in the nuclear export of viral mRNAs.

Finally, the NS1 protein functionally interacts with the viral polymerase complex in infected cells and likely has a role in the regulation of viral RNA synthesis.

Further reading:

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Influenza pandemic

In the last 100 years there have been three major influenza pandemics: Spanish Flu in 1918, Asian Flu in 1957 and Hong Kong Flu in 1968. These claimed the lives of approximately 50 million, 2 million and 1 million people respectively. Added to this is the annual death toll of 250,000 to 500,000 people worldwide with a further 3 to 4 million people suffering severe illness. These statistics make influenza an extremely important pathogen.

In 1997 the alarming emergence of a new, highly pathogenic subtype, H5N1, which has a 50% mortality rate, provided a major impetus for renewed influenza research. However the battle against influenza is going to be difficult. Recently another subtype, H1N1, has emerged. This subtype causes a relatively mild infection in humans, however is highly transmittable between people and a new influenza pandemic was declared by the World Health Organization. If this virus were to acquire some of the lethal capabilities of H5N1, then the ensuing pandemic could be devastating.

Further reading:

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RNAi Gene Therapy to Control Respiratory Viral Infections

Pathogenic respiratory viruses, exemplified by respiratory syncytial virus (RSV), influenza (Flu) and parainfluenza virus (PIV), are major disease agents that kill millions of humans worldwide. Other respiratory viruses that are also potential agents of bioterrorism include highly pathogenic avian flu virus, SARS coronavirus, and the henipaviruses. Respiratory infection by RSV and PIV is the most prevalent cause of pediatric hospitalization in industrialized Western nations. In the US alone, it leads to about 100,000 admissions per year at a cost of about $300 M.

The lack of a reliable vaccine or antiviral against these viruses, in part due to the high mutation rate of the viral RNA genomes, has led to the adoption of the novel RNA interference (RNAi) strategy. There has been significant recent progress in the development of RNAi therapeutics to defeat these viral respiratory diseases.

Further reading:

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RNAi Gene Therapy to Control Hepatitis C

Hepatitis C virus (HCV) is a leading cause of chronic hepatitis and its sequels, end-stage liver disease and hepatocellular carcinoma, are the most common indications for liver transplantation. The current standard treatment, pegylated-interferon-alpha in combination with ribavirin, represents a milestone in therapy, but only eradicates the virus in half of the patients, leaving tens of millions without hope for a cure. Therefore, it is urgent to explore novel and more effective therapeutic options. Such advancements could be derived from a better understanding of HCV biology. Progress in this area has accelerated with the application of RNA interference (RNAi) as a discovery tool to investigate viral and host cell factors involved in viral infection. Furthermore, RNAi has high potential as a therapeutic avenue for treatment of HCV.

Further reading:

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RNAi to Treat Chronic Hepatitis B Virus Infection

Chronic infection with the hepatitis B virus (HBV) occurs in approximately 6% of the world's population and carriers of the virus are at risk for complicating hepatocellular carcinoma (HCC) and cirrhosis. Although effective vaccination is available, it is prophylactic and of little use to individuals who are already infected with the virus. Furthermore, current treatment options have limited efficacy and chronic HBV infection is likely to be a significant global medical problem for many years to come.

Silencing HBV gene expression by harnessing RNA interference (RNAi) presents an attractive option for development of novel and effective anti HBV agents. Numerous studies have reported highly successful suppression of viral replication, which bodes well for employing this approach to counter HBV infection. However, despite significant and rapid progress, further refinement of existing technologies is necessary before clinical application of RNAi-based HBV therapies is realised. Improvement of delivery efficiency, dose regulation, limiting of off target effects and preventing reactivation of viral replication are some of the hurdles that need to be overcome. Nevertheless, the vast potential of RNAi-based therapeutics will continue to drive innovative research, and this promises to surmount the obstacles that face this exciting field.

Further reading:

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RNAi Gene Therapy to Control HIV-1 Infection

RNA interference (RNAi) was discovered as cellular gene regulation mechanism in 1998, but several RNAi-based applications for gene silencing have already made it into clinical trials. RNAi approaches have targeted pathogenic human viruses causing acute or chronic infections. HIV-1 infection has been considered for RNAi-based gene therapy. Viruses like HIV-1 are particularly difficult targets for RNAi-attack because they are escape-prone, which requires combinatorial RNAi strategies to prevent viral escape. The future of antiviral RNAi therapeutics is very promising, but it remains of critical importance to include many controls in pre-clinical test models to unequivocally demonstrate sequence-specific action of the RNAi inducers.

Further reading:

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Viral Escape From RNAi in Mammalian Cells

Recent studies regarding the utility of RNAi to specifically inhibit virus replication have opened new possibilities for the development of novel therapies against viral infection. However, viruses appear to be capable of escaping RNAi inhibition in mammalian cells. Viral mechanisms for escaping RNAi may include suppression of RNAi, mutational escape from RNAi, and modulation of the cell's microRNA (miRNA) /RNAi profile.

Further reading:

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Virus-encoded Suppressors of RNA Silencing

Small RNA-directed silencing mechanisms play important roles in the regulation of eukaryotic gene expression. In plants, insects, nematodes and fungi RNA silencing mechanisms are also involved in innate antiviral defence responses. To counter antiviral RNA silencing, viruses from plants, insects and fungi encode RNA silencing suppressors (RSSs).

Recent studies suggest that RNA silencing in mammals, or RNA interference (RNAi), is also involved in antiviral responses. In particular, there is increasing evidence that cellular regulatory microRNAs (miRNAs) have a function in restricting virus replication in mammalian cells. Similar to plant and insect viruses, several mammalian viruses encode RSS factors that inhibit the RNAi mechanism. Several of these suppressors are multifunctional proteins that were previously shown to block innate antiviral immune responses involving the interferon (IFN) pathway.

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Virus-encoded MicroRNAs

The discovery that viruses could encode micro (mi)RNAs, similarly to the eukaryotic organisms they infect, has opened new perspectives in the study of host-virus interactions. These small regulatory RNAs, which are critically involved in an ever-increasing number of biological processes, have revolutionized the way we used to see gene regulation. Some mammalian viruses, mainly from the herpesvirus and polyomavirus families, have hijacked this mechanism in order to help them achieve the infection of their host ... read more

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Dengue disease

Dengue disease is caused by the four serotypes of mosquito-borne dengue virus (DENV1-4), positive-sense RNA viruses belonging to the genus Flavivirus. Escalation of the dengue pandemic can largely be attributed to three factors: (i) increased urbanization and consequent urban detritus and population density leading to enhanced vector breeding and increased contact between humans and vectors, (ii) global invasion of the major mosquito vectors, Aedes aegypti and Aedes albopictus, leading to geographic spread and geographic overlap of all four dengue virus serotypes and (iii) interaction and evolution of the four serotypes themselves, resulting in greater disease severity. As a result of these changes, DENV is now the most common arboviral infection of humans in the subtropical and subtropical regions of the world. The World Health Organization (WHO) estimates that 2.5 billion people are risk from dengue with 50 million dengue infections worldwide every year. In 2007, there were more than 890,000 reported cases of dengue in the Americas, approximately 26,000 of which were the most severe form, dengue haemorrhagic fever (DHF). The WHO reports that dengue disease is endemic in more than 100 countries in Africa, the Americas, the Eastern Mediterranean, South-East Asia and the Western Pacific, with South-East Asia and the Western Pacific the most seriously affected. Approximately 500,000 people with DHF require hospitalization each year, of whom 2.5% die.


from Endy et al. in Frontiers in Dengue Virus Research

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Dengue virus epidemiology

The spread of Aedes aegypti mosquitoes through the slave trade and later through the movement of ships and goods during the Second World War facilitated the global expansion of dengue virus. The first descriptions of dengue fever characterized the eighteenth-century pandemic of dengue infection as described in 1780 by Benjamin Rush during a large outbreak of dengue fever in Philadelphia, Pennsylvania, in the USA. Dengue was thought to have been introduced in the USA as a consequence of the rum and slave trade between Africa and Caribbean ports. Dengue outbreaks occurred throughout the USA, the Caribbean and South America during the nineteenth and early twentieth centuries. The second dengue pandemic was centred in the mining towns of northern Queensland, Australia, where boom towns and resulting Aedes aegypti population growth resulted in continuous dengue transmission from the 1870s until the First World War. Dengue outbreaks were also occurring in the Eastern Mediterranean and resulted in a large epidemic in Greece during 1928. During the Second World War, dengue strains were carried by ships and soldiers from South-East Asia to Japan, the Pacific Islands, Philippines and Hawaii. A new manifestation of severe dengue illness resulted, dengue haemorrhagic fever, first reported in the Philippines then later in Thailand during the 1950s.

The discovery of the role of Aedes aegypti in the transmission and spread of yellow fever and the subsequent isolation of the virus and creation of an effective yellow fever vaccine introduced the concept of mosquito control as an effective measure to disrupt yellow fever transmission. Subsequently the International Health Board and the Rockefeller Foundation instituted mosquito control strategies including the use of a larvicidal, Paris Green, throughout the USA and Central and South America. These techniques were soon applied to malaria control and during the years from 1924 to 1925, funding for malaria prevention through the strategy of mosquito control doubled. The success of this programme in Italy during the 1920s set the stage for the global use of mosquito control in the prevention of malaria. The Second World War prompted the creation of the Rockefeller Foundation Health Commission in 1942 to support national defence and in particular malaria control for U.S. forces. The need for lousicides to combat typhus ushered in a new insecticide developed by the Swiss firm, Geigy, called dichlorodiphenyl-trichloroethane (DDT). Led by Fred Soper, the Rockefeller team demonstrated the effectiveness of DDT as a lousicide and in disrupting typhus epidemics. DDT was soon used in aerial and ground spraying for Allied Forces during a malaria outbreak in Italy and was found to be a highly effective larvicide with a long environmental persistence. DDT subsequently became a key component of the World Health Organization's global malaria eradication campaign in 1955. This campaign resulted in the elimination of both the malaria mosquito vector and Aedes aegypti throughout South America and the virtual elimination of malaria, yellow fever and dengue throughout the Americas. A reassessment of this global strategy by the WHO and the growing concerns of the environmental effects of DDT led to the end of the use of DDT as a mosquito control larvicide in 1969. The cessation of DDT-based mosquito control programmes in the Americas and the social disruption that resulted from the Second World War allowed the spread of DENV in Asia, the reintroduction and resurgence of Aedes aegypti throughout the Americas and, consequently, resurgence of DENV, particularly South-East Asian strains, in the Americas.

The first two dengue pandemics were characterized by epidemics that produced severe outbreaks of fever, headache and myalgias, a clinical syndrome termed dengue fever. As waves of DENV-1 to -4 spread throughout the human population, especially in Asia, DENV adapted to be able to reach virus levels during a course of infection that allowed mosquitoes to become infected, thereby ensuring continued transmission of the virus. There is variation among vector species in their susceptibility to dengue and the potential selective effects of such variation on viral replication; however, high levels of co-circulation among serotypes also posed a challenge for the persistence of each serotype. Consider a DENV-2 strain entering a population that had a high degree of pre-existing antibody to an established DENV, such as DENV-1. Preexisting DENV-1 antibody, though not neutralizing, would under ordinary circumstances have provided significant heterotypic neutralization of DENV-2, potentially reducing viral levels in infected humans and thereby interrupting mosquito transmission. Thus, the presence of high levels of infection by multiple serotypes imposed significant selection for viruses that, via mutations in the E protein coat and changes in specific epitopes, were able to either fully escape the effects of heterotypic neutralization, or as is currently thought to be the case, to utilize these subneutralizing antibodies to enhance infection. This phenomenon of viral replicative enhancement due to subneutralizing heterotypic antibody is known as antibody-dependant enhancement (ADE). Since ADE results in higher viral loads, viruses with a particularly high tendency towards enhancement should have a selective advantage.

The ability of all DENV serotypes to utilize pre-existing heterotypic flavivirus antibody to enhance infection is a unique feature of DENV that is particularly common among South-East Asian strains. The tendency to be enhanced by heteroserotypic antibody distinguishes DENV from all other flaviviruses, and is the primary basis of DENV pathogenesis in severe dengue illness. During the third pandemic, this tendency of DENV to be enhanced in secondary dengue infection resulted in the clinical manifestation of a previously unrecognized sequelae of DENV infection - severe haemorrhagic disease and plasma leakage. First described as Philippine and Bangkok haemorrhagic fever during the 1950s, it is now recognized as dengue haemorrhagic fever (DHF).

from Endy et al. in Frontiers in Dengue Virus Research

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Studies of dengue in Thailand

During the 1950s, the South-East Asian Treaty Organization (SEATO), in response to a cholera outbreak occurring throughout Asia, created a number of laboratories comprised of host-country and US scientists in Thailand, Malaysia, Bangladesh and Pakistan. The Thailand laboratory named the SEATO General Medical Research Project located in Bangkok, later re-named the Armed Forces Research Institute of Medical Sciences (AFRIMS) in 1977, formed a still ongoing 50-year relationship of Thai-US collaborators in the study of tropical infectious diseases. The discovery that Bangkok was experiencing an outbreak of a new clinical manifestation of dengue infection, dengue haemorrhagic fever by both Thai and US scientists, allowed the ongoing study of dengue in Thailand that spanned over a half of a century producing many of the seminal concepts of dengue virus transmission and disease severity. Early studies on DHF in Thailand established this as a unique clinical syndrome of DENV infection. Careful clinical studies of hospitalized children in Bangkok, Thailand demonstrated the clinical severity of DHF in producing thrombocytopenia, leucopenia, coagulopathy and plasma leakage. Studies on DHF pathogenesis in the 1960s revealed its unique features in being largely a phenomenon of secondary DENV infections or in primary infection of infants, a function of declining maternal DENV antibody. Classic studies in Thai children first established the role of enhancing antibody in the peripheral blood mononuclear cells of children in producing severe dengue illness and DHF. Prospective studies in hospitalized Thai children and in long-term cohort studies demonstrated the importance of dengue viral load and the T-cell response in determining dengue severity, the diversity of all four dengue serotypes circulating spatially and temporally in a well-defined geographic area and the role of subclinical dengue infection and its contribution to the overall burden of dengue illness.

from Endy et al. in Frontiers in Dengue Virus Research

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Dengue virus evolution

The evolutionary path of dengue virus differs in several important aspects from its flavivirus cousins, though dengue retains many of the same clinical characteristics such as production of severe fever, myalgias, headache, hepatitis, encephalitis and haemorrhage. The phylogeny of the flaviviruses sheds little light on the origin of DENV because the closest relatives include mosquito-borne viruses that occur in several continents. However, as described by Vasilakis, more detailed phylogenetic studies of DENV suggest an Asian origin, where sylvatic cycles between non-human primates and Aedes mosquitoes arose. Unlike the other flaviviruses however, DENV evolved into four antigenically and phylogenetically distinct serotypes: DENV-1, DENV-2, DENV-3 and DENV-4. Subsequently, each of these four serotypes emerged independently into an endemic cycle of transmission between humans and Aedes albopictus. This endemic cycle is now both ecologically and evolutionarily separate from the sylvatic cycle. Thus, unlike other flaviviral pathogens, urban cycles of DENV can no longer be considered zoonotic.


It has been demonstrated that DENV evolves according to a molecular clock at a serotype- and genotype-specific rate, and that the transfer of DENV from a sylvatic cycle to sustained human transmission may have occurred on the order of 100 to 1500 years ago years ago, suggesting that the current global pandemic of all four serotypes of DENV appeared during the past century. The contemporary genetic diversity seen in all four dengue serotypes is related to population growth, urbanization, and mass transport of both virus and its mosquito vector. Using an analytical technique based on coalescent theory, it was demonstrated that DENV-2 and DENV-3 experienced two phases of exponential growth. In the first phase and for most of their history, the dengue viruses experienced a low rate of exponential growth. Thirty years ago, the rate of growth of DENV-2 and DENV-3 suddenly increased by a factor of between 15 and 20.

from Endy et al. in Frontiers in Dengue Virus Research

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Evolution of the flaviviruses

It is not known with certainty when and where the progenitor of the approximately 80 species in the genus Flavivirus first arose, although geographic evidence suggests that this ancestral flavivirus may have first appeared in Africa. Over the course of speciation, the flaviviruses have shown substantial ecological diversification. Most notably, different lineages of flaviviruses adapted to different modes of transmission. A current phylogenetic tree of the genus Flavivirus shows that the basal-most lineages are viruses that have only been isolated from mosquitoes and are not known to infect vertebrates at all. This suggests that the ancestor of the genus may have been a 'mosquito-only' virus that later acquired the ability to infect vertebrates.

The remaining flaviviruses are divided into vector-borne viruses of vertebrates, with major groups using ticks and mosquitoes for horizontal transmission, and another group that infects vertebrates without the use of arthropod vectors. This topology does not suggest whether vector-borne or non-vectorborne transmission was ancestral, but the basal position of the 'mosquito-only' viruses suggests that mosquito-borne transmission among vertebrates may have preceded the loss of vector transmission. Tick-borne transmission may have evolved from a mosquito-borne lineage after the lineage that infects only vertebrates arose.

from Endy et al. in Frontiers in Dengue Virus Research

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Book review: ABC Transporters

from Britta Kunert in Webcritics.de

ABC transporters in Microorganisms is an excellent summing up of data from structural, biochemical as well as clinical investigations of ABC transporters. The main focus is drawn on multidrug resistance-linked members of this protein superfamily.... read the full review

This book is a comprehensive review with a general outline given in each chapter that is essential and useful not only for readers interested in the fascinating ABC transporter family. ... read the full review

Full details about this book: ABC Transporters in Microorganisms

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HTLV and HIV

For many years, retroviruses were known to be the cause of many kinds of animal leukemias and hematopoietic tumors. In spite of the high expectation that this would also be true for humans, very little evidence for retroviral involvement in any human diseases was forthcoming.

In the late 1970s, however, due to the development of sensitive and specific molecular methods to identify retroviruses and to produce large scale cultures of T lymphocytes, HTLV-I was discovered and implicated as the cause of adult T cell leukemia, a particular and relatively infrequent leukemia prevalent in southern Japan and parts of the Caribbean, and tropical spastic paraparesis, a demyelinating neuropathy similar to multiple sclerosis. The discovery that HTLV-I can be transmitted by breast milk has led to a significant decline in HTLV-I infections in Japan.

Although no retroviruses have been identified to date in other human leukemias or related diseases, the efforts that resulted in the discovery of HTLV-I were critical in isolating HIV-1 and identifying it as the cause of AIDS. The ability to grow the HIV-1 in quantity allowed the development of a blood test that has saved countless lives. The development of effective anti-retroviral drugs has made HIV-1 infection a somewhat manageable chronic condition rather than a certain death sentence. Although vaccine trials thus far have been rather disappointing, an effective vaccine is one of our most important needs.

Further reading: Retroviruses: Molecular Biology, Genomics and Pathogenesis

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Simian Exogenous Retroviruses

Simians include diverse species of monkeys which are globally distributed predominantly in the southern hemisphere, and ape species that are restricted to the rainforests of central Africa and Southeast Asia. Types of simian retroviruses have been detected in almost all species of non-human primates which have been studied. As early identification and classification of primate retroviruses was largely possible due to the efforts to establish cell lines from various primate species, there were limitations.

Firstly, the search for simian retroviruses was frequently restricted to only a few species cell lines. Secondly, not all retroviruses were permissive to the available cell lines due to species specific restriction or cell-type specific factors. The earliest discoveries of simian retroviruses were often based on a specific observations which arose from diagnostic workups of cases of then undefined illness or unusual cancers. This chapter focuses on the four main groups of exogenous simian retroviruses; type D simian retroviruses (SRV), simian foamy viruses (SFV) commonly known as spumaviruses, the simian T-cell lymphotropic viruses (STLV), and the expanding group of simian immunodeficiency viruses (SIV).

Initially viruses in these subgroups of simian retroviruses were identified based on the diseases from which they were associated with. Retroperitoneal firbrosarcomas and chronic wasting disease led to the early identification of the SRVs, found to be associated with a spectrum of diseases in different species of macaques. Other simian retroviruses are frequently asymptomatic in their natural hosts and in some cases simply cause cytopathic effect (CPE) in cell culture (SFV).

In the last two decades molecular techniques have provided us with much more insight into the phylogeny of the wide variety of diverse retroviruses, knowledge which has enriched the seroprevalence evidence of widespread retroviral infections in many different primate species.


Further reading: Retroviruses: Molecular Biology, Genomics and Pathogenesis

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Mammalian and Fish Retroviruses

The pioneering phase of the study of retroviruses resulted in the identification of viruses associated with diseases in chickens, mice and cats. Retroviruses have since been isolated from many vertebrate species, and classified into seven genera that can be grouped into two general categories.

Alpharetroviruses, betaretroviruses and gammaretroviruses are genetically simple, encoding only nucleoprotein, matrix, capsid, reverse transcriptase, integrase, protease and envelope proteins. Deltaretroviruses, epsilonretroviruses, lentiviruses and spumaviruses are considered complex because they encode in addition to the proteins listed above, a number of ancillary proteins that often play an important role in gene regulation.

Simple mammalian gammaretroviruses and the complex piscine epsilonretroviruses and bovine leukemia virus have shed light on the mechanisms of viral function, evolution and pathogenesis within the animal kingdom that hosts them.

Further reading: Retroviruses: Molecular Biology, Genomics and Pathogenesis

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Retroviral Vectors for Gene Delivery

Gammaretroviral and lentiviral vectors for gene therapy have been developed that mediate stable genetic modification of treated cells by chromosomal integration of the transferred vector genomes. This is highly desired, not only for research use, but also for clinical gene therapy aiming at the long-term correction of genetic defects, e.g., in stem and progenitor cells.

Retroviral vector particles with tropism for various target cells have been designed. Due to split genome vector design the risk of replication-competent retrovirus formation has been minimized. Gammaretroviral and lentiviral vectors have so far been used in more than 300 clinical trials, addressing treatment options for various diseases. In some cases these trials resulted in benefit for treated patients suffering from life threatening disease.

Insertional mutagenesis due to vector integration in or next to cellular proto-oncogenes was concluded to be necessary for the lymphoproliferative disease observed in some patients treated with gammaretrovirally modified haematopoietic stem cells for X-linked severe combined immunodeficiency disease. These findings prompted the design of gammaretroviral vectors harbouring self-inactivating (SIN) Long Terminal Repeats (LTRs), which current lentiviral vectors already have.

SIN vectors may reduce the effect of insertional mutagenesis and proto-oncogene activation, thereby reducing the risk of oncogenesis. With a view to future clinical use, new developments such as cell entry targeting will further improve the safety and efficacy of retroviral vectors.

Further reading:
Retroviruses: Molecular Biology, Genomics and Pathogenesis
Lentiviruses and Macrophages: Molecular and Cellular Interactions

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Retroviral Vaccines

The failure of 'classical' vaccines to induce protection to the most important of all retroviruses, HIV, has led to the development of a huge variety of 'molecular vaccines', i.e. vaccines produced using modern molecular biological techniques. Such vaccines range from simple plasmid DNA coding for the genes of choice, through recombinant viruses carrying such genes to engineered bacteria designed to deliver HIV genes to the mucosal immune system.

Evaluation of AIDS vaccines has resulted in sporadic successes and many failures and the few human clinical trials have been, at best, negative. However, the relative success of molecular vaccines in combating other retroviral infections and the continuing refinement of HIV/SIV vaccines showing some efficacy suggests that a molecular AIDS vaccine may be achievable. In the end, the HIV/AIDS pandemic will only be defeated by the development of an effective, stable, and inexpensive vaccine.

Further reading:
Retroviruses: Molecular Biology, Genomics and Pathogenesis
AIDS Vaccine Development: Challenges and Opportunities

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Retroviral Restriction Factors

Over the course of the retrovirus replication cycle, viral cDNA is inserted into host chromosomal DNA to establish the provirus. This process results in a permanent insertion mutation in the host cell genome. Host cells have evolved intracellular factors that block the spread of retroviral infection. Some of these antiviral factors act prior to integration and therefore also block the mutagenic potential of infection.

Several such factors have been identified, including Fv1, the APOBEC3 complex, and TRIM5. These host factors potently block HIV-1 and other retroviruses from establishment of the provirus. Here we will review current understanding of Fv1, APOBEC3, and TRIM5 proteins, with particular emphasis on TRIM5.

Further reading: Retroviruses: Molecular Biology, Genomics and Pathogenesis

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Pathogenesis of Immunodeficiency Virus Infections

Extensive analysis of naturally occurring simian immunodeficiency viruses (SIVs) and comparative phylogenetic studies with human immunodeficiency viruses (HIVs) suggests that the latter are close relatives of the SIVcpz viruses of chimpanzees (HIV-1) or the SIVsmm viruses of sooty mangabys (HIV-2).

Crossing of species barriers resulted in adaptation to the human host and subsequent acquisition of a pathogenic phenotype. Naturally occurring T lymphocyte-tropic lentiviral infections are highly prevalent and productive but are not usually pathogenic for native hosts. Crossing species barriers may produce an abortive infection or, as in the case of the HIVs, may enhance virulence after several cycles of transmission.

The large number of species carrying these viruses may suggest that infection confers an evolutionary advantage to the host. The virulent T-lymphocyte-tropic lentiviruses have a similar genomic structure and exhibit comparable replication strategies. Their major targets are lymphocytes populating lymphoid organs and tissues, and antigen-presenting cells (dendritic cells, mononuclear phagocytes). Within these targets the virus can replicate to very high titres and thereby exhaust CD4+ T cells, producing profound immunodeficiency. Although the infection of lymphoid organs and tissue is the pathologic hallmark of HIV infection, this virus also infects cells of the central nervous system

Further reading: Retroviruses: Molecular Biology, Genomics and Pathogenesis

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Pathogenesis of Oncoviral Infections

Retroviruses cause cancer in natural or laboratory settings by a variety of mechanisms. The acutely transforming or transducing retroviruses induce tumours in animals within days to weeks. They harbour a host-cell derived gene, an oncogene, which infiltrate signalling cascades that regulate cell growth and survival.

The oncoprotein encoded by the viral oncogene is activated to dominant signalling, either by deregulated expression or as a result of a modified protein structure that uncouples downstream signalling from upstream physiological signals. The cis-acting or non-acutely transforming viruses cause disease with latency periods of months. These viruses work as insertional mutagens to promote multi-step oncogenesis, and large-scale mapping of proviral insertions in tumour DNAs provides a rich source of candidate genes with a potential role in cancer of non-retroviral aetiology.

Viral proteins may also stimulate target cells to proliferate. One example is the mouse mammary tumour virus which stimulates lymphocytes via a virus-encoded superantigen. Other examples are the mitogenic stimulation of erythrocyte precursor cells by the defective envelope protein of the mouse spleen focus-forming virus, and the direct oncogenic affect of the envelope protein of the Jaagsiekte sheep retrovirus.

Further reading: Retroviruses: Molecular Biology, Genomics and Pathogenesis

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Reverse Transcription

Retroviruses are unique among animal viruses in that their replication requires the recombination of their own genetic material with that of the infected host cell. Two virus-encapsulated enzymes, reverse transcriptase and integrase, are dedicated to provirus formation.

Reverse transcriptase, using a packaged cellular tRNA primer to initiate DNA synthesis from the viral RNA template, generates linear double-stranded DNA within the context of the reverse transcription nucleoprotein complex. The integrase enzyme processes the neo-synthesised DNA ends as the preintegration complex moves toward the cell nucleus.

After finding a suitable chromatin acceptor site, the integrase recombines the processed DNA ends with a cell chromosome. For further details on the mechanisms of viral DNA synthesis, its transport to the nucleus, and the resulting chromosomal DNA integration please read Chapter 5 Reverse Transcription and Integration by Alan Engelman in Retroviruses: Molecular Biology, Genomics and Pathogenesis


Further reading: Retroviruses: Molecular Biology, Genomics and Pathogenesis

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Endogenous retroviruses

Endogenous retroviruses are genetic elements representing the result of retrovirus infections and integration of the proviruses into the germline of vertebrates including humans. Retroviruses use the enzyme reverse transcriptase (RT) to transcribe their RNA genome into cDNA and incorporate it into the cellular genome. Infections of germ cells result in the presence of these viruses in the genome all cells of the organism and transmission of these sequneces to the offspring.

Only some endogenous retroviruses are replication competent and produce infectious particles; most are defective. Although the role of endogenous retroviruses during tumour development and autoimmune diseases is still unclear, sufficient evidence has accumulated indicating that retroviruses play an important role in physiological processes.

Endogenous retroviruses are involved in placental differentiation and immunosuppression during pregnancy, and retroviral long term repeats (LTR) regulate the expression of cellular genes. During evolution three main processes took place: First, an accumulation of defective proviral DNA ("junk DNA"), second a development of stronger restriction strategies by the host and third, an utilisation, "enslavement" of retroviral genes and LTRs.

Since transspecies transmissions of retroviruses are very common, endogenous retrovirus may be important also for the health of other species. For example, pig cells can release porcine endogenous retroviruses that infect human cells and therefore represent a risk for xenotransplantations involving pig cells or organs.

Further reading: Retroviruses: Molecular Biology, Genomics and Pathogenesis

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Retrotransposons

Many classes of transposons and retrotransposons have invaded and shaped the genomes of their metazoan hosts. Class I transposons (i.e. retrotransposons) include both elements which contain long terminal repeats (LTRs) and many others lacking LTRs.

Along with retroviruses, retrotransposons share a fundamental mechanism of mobilisation through reverse transcription of an RNA template, via enzymatic activity of a reverse transcriptase.

Unlike retroviruses, retrotransposons remain entirely intracellular during their life cycle. Several distinctive and overlapping genome defense mechanisms have been developed over evolutionary time, as host organisms have fought back against these mobile retroelements. The ongoing conflict between these myriad genomic parasites and their widespread host organisms has resulted in positive and deleterious consequences including exaptation, genomic deletions, certain diseases including cancers, and the generation of diversity probably including the formation of new species.

Further reading: Retroviruses: Molecular Biology, Genomics and Pathogenesis

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Retroviruses

Retroviruses comprise a diverse family of enveloped RNA viruses, remarkable for their use of reverse transcription of viral RNA into linear double stranded DNA during replication and the subsequent integration of this DNA into the genome of the host cell. Members of this family include important pathogens such as HIV-1, feline leukemia, and several cancer-causing viruses.

Research into retroviruses led to the discovery of oncogenes, a major advance in the field of cancer genetics. Studies of retroviruses have contributed greatly to our understanding of mechanisms that regulate eukaryotic gene expression.

Retroviruses are proving to be valuable research tools in molecular biology and have been used successfully in gene therapy (e.g. to treat X-linked severe combined immunodeficiency).

Further reading: Retroviruses: Molecular Biology, Genomics and Pathogenesis

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Aspergillus infections

Aspergillus fumigatus and other species capable of growing at 37°C are opportunistic pathogens. About 40 of the 250 species of Aspergillus have been reported as human pathogens but the majority of cases are associated with just one species: A. fumigatus. The respiratory system is the normal portal of entry. The animal diseases caused by Aspergillus infection are all lumped together under the term 'aspergillosis.' Aspergillosis is a 'big umbrella' term, with an accompanying enormous literature. It refers to all infections caused by Aspergillus, including both veterinary and human disease, and ranging from localized and minor maladies to those that are systemic and life threatening. Although not contagious, human aspergillosis is of growing importance in modern medical care. Aspergillosis has been reported from all species of domestic animals and many wild species. Birds show a particularly high susceptibility; historically, aspergillosis was first recognized as an avian disease.

Different forms of aspergillosis include severe asthma with fungal sensitization; 'fungus ball,' (aspergilloma) whereby the mould colonizes usually without spreading, causing a gramulomatous disease of the lung; and systemic (invasive) aspergillosis, in which the fungus disseminates throughout the body. Aspergilloma and invasive aspergillosis both involve direct growth of the fungus inside of host tissues; the former is often found associated with tuberculosis and is 'semi-invasive.' Invasive aspergillosis, also called systemic aspergillosis, is the most life threatening form of Aspergillus infection. The clinical categorization of these conditions defies neat classification but provide a good introductory framework for understanding aspergillosis. Despite advances in antifungal drug therapy, the invasive forms of aspergillosis have extremely high mortality rates.

Clinical manifestations and the severity of aspergillosis reflect the immunological status of the patient. The best protection is a robust immune system. Dissemination of Aspergillus in the body indicates a break of, or deficiency in, host defences. Immunosuppressive agents and other medical developments have created a new ecological niche for aspergilli to grow on people with impaired immune systems, where they can cause serious and often fatal infections. Invasive aspergillosis, with an attendant high mortality rate, has become increasingly common as the number of susceptible hosts is increased. Bone marrow recipients constitute particularly vulnerable populations. Unfortunately, drug resistance to known antifungal drugs is becoming more common. As the disease has become more prevalent, there is a great need for expanding the number of safe and more reliable anti fungal drugs.

The early diagnosis of invasive Aspergillus infections is still difficult. It is usually based on the isolation and subsequent identification of species from appropriate clinical specimens and/or the detection of characteristic septate hyphae in sections of tissue following biopsies. Unfortunately, disseminated aspergillosis is frequently not diagnosed until necropsy. Another growing problem is the increasing number species causing invasive aspergillosis in organ transplant patients. Many of these 'non-fumigatus' aspergilli are resistant to the drugs commonly usually used to treat aspergillosis. A. flavus, the second most common species involved in invasive aspergillosis, is the most common cause of superficial infection.

A good definition of human pathogen is 'a microbial or parasitic species that can infect and is capable of causing disease in humans under natural transmission conditions'. The best-known bacterial pathogens have co-evolved with their hosts to subvert host functions and they possess special virulence factors that have indispensable functions in mediating host-pathogen interactions. Aspergillus infections do not resemble classical bacterial diseases. A. fumigatus has no obvious need for passage in humans or other animals. The fact that Aspergillus can become a deadly pathogen may be a biological accident associated with it extreme opportunism. With invasive aspergillosis, the immunological status of the host - not the virulence of the fungus - is the single most significant element. Despite intensive study, the molecular basis of the pathogenic potential of A. fumigatus remains elusive. Suggested reading: Medical Mycology Publications

In summary, as disease categories go, aspergillosis is an extremely capacious rubric. Occupational mycoses, allergies, localized mycoses, and invasive mycoses are all assembled together under the same name. 'Aspergillosis' encompasses any and all medical and veterinary diseases caused by any and all members of the genus Aspergillus. The word 'aspergillosis' describes so many different clinical entities that, without qualifications, the term is almost meaningless. It would be useful if we did a better job of stipulating definitions for the various specific diseases grouped together under the aspergillosis rubric. Hypersensitivity reactions are not the same as fungus ball. Invasive aspergillosis is profoundly different from both. Further, there is growing evidence that 'non-fumigatus' Aspergillus infections have different manifestations other than their patterns of differential drug resistance. One of our greatest challenges in studying aspergillosis may be to break conventional mindsets about the nature of pathogenicity. As the numbers of immune suppressed individuals increase within the human population, cases of invasive aspergillosis are bound to increase too and they will become a mounting burden on our health care systems. Suggested reading: Medical Mycology Publications

Adapted from An Overview of the Genus Aspergillus by Joan W. Bennett writing in Aspergillus: Molecular Biology and Genomics

Further reading

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Mycotoxins

In agriculture, Aspergillus originally was considered a serious problem largely because of its prevalence in the biodeterioration of stored crops and as an opportunistic pathogen of field crops, particularly under high moisture conditions. During the early 1960s, the discovery of aflatoxins associated with massive deaths of poultry, trout and other domesticated animals species worldwide raised new awareness that these fungi posed threats to foods and feeds beyond their ability to rot plant materials. Research on aflatoxins led to a so-called 'golden age' of mycotoxin research during which many new fungal toxins were discovered from species of Aspergillus and other common moulds. In addition to aflatoxins, other important Aspergillus mycotoxins include ochratoxin, patulin and fumigillin. Suggested reading: Microbial Toxins and Microbial Biodegradation

Aflatoxins are still recognized as the most important mycotoxins. They are synthesized by only a few Aspergillus species of which A. flavus and A. parasiticus are the most problematic. The expression of aflatoxin-related diseases is influenced by factors such as age, nutrition, sex, species and the possibility of concurrent exposure to other toxins. The main target organ in mammals is the liver so aflatoxicosis is primarily a hepatic disease. Conditions increasing the likelihood of aflatoxicosis in humans include limited availability of food, environmental conditions that favour mould growth on foodstuffs, and lack of regulatory systems for aflatoxin monitoring and control. Suggested reading: Foodborne Pathogens: Microbiology and Molecular Biology

A. flavus and A. parasiticus are weedy moulds that grow on a large number of substrates, particularly under high moisture conditions. Aflatoxins have been isolated from all major cereal crops, and from sources as diverse as peanut butter and marijuana. The staple commodities regularly contaminated with aflatoxins include cassava, chillies, corn, cotton seed, millet, peanuts, rice, sorghum, sunflower seeds, tree nuts, wheat, and a variety of spices intended for human or animal food use. When processed, aflatoxins get into the general food supply where they have been found in both pet and human foods as well as in feedstocks for agricultural animals. Aflatoxin transformation products are sometimes found in eggs, milk products and meat when animals are fed contaminated grains. Suggested reading: Foodborne Pathogens: Microbiology and Molecular Biology

Human exposure to aflatoxins exposure is difficult to avoid because A. flavus grows aggressively in many foods at all stages of the food chain: in the field, in storage and in the home. Evidence for acute human aflatoxicosis has been reported from several underdeveloped countries such as India and Thailand. The symptoms of severe aflatoxicosis include oedema, hemorrhagic necrosis of the liver and profound lethargy. Further, aflatoxins are potent carcinogens, especially aflatoxin B1. Based on epidemiological studies done in Asian and Africa, in 1988 the International Agency for Research on Cancer, part of the World Health Organization, placed aflatoxin B1 on the list of human carcinogens. In developed countries, the emphasis on keeping aflatoxin out of the food chain concerns its carcinogenic potential. Strong regulatory limits (4-30 ppb) have been established for many commodities. Suggested reading: Microbial Toxins: Current Research and Future Trends

Adapted from An Overview of the Genus Aspergillus by Joan W. Bennett writing in Aspergillus: Molecular Biology and Genomics

Further reading

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Aspergillus and disease

Aerosolized Aspergillus spores are found nearly everywhere so we are routinely and almost constantly exposed to them. Such exposure is a normal part of the human condition and generally poses no adverse health effects. Nevertheless, Aspergillus can and does cause animal disease in three major ways: through the production of mycotoxins; through induction of allergenic responses; and through localized or systemic infections. With the latter two categories, the immune status of the host is pivotal. Allergies and asthma are thought to be caused by an active host immune response against the presence of fungal spores or hyphae. In contrast, with invasive aspergillosis, the immune system has collapsed and little or no defence can be mounted. Suggested reading: Microbial Toxins: Current Research and Future Trends

Allergies and asthma

Atopy is a genetic predisposition to developing certain hypersensitivity reactions such as asthma, hay fever (allergic rhinitis), and food allergies. Allergic reactions to Aspergillus in atopic individuals can be caused by fungal spores in the air and from fungi ingested in food. Airborne spores are readily inhaled when we breathe; they also come into contact with the eyes and other exposed parts of the body. Moulds are involved in the initiation and exacerbation of lower airway diseases such as asthma, although the specific aetiology is poorly understood.

The level of spore inhalation varies enormously with local environmental conditions. Certain environments like compost heaps and barns have unusually high concentrations. Massive exposure, even among individuals who are not allergic or asthmatic, should be avoided because repeated contact with large doses of fungal spores may induce allergic alveolitis, in which a lymphocyte-directed hypersensitivity reaction occurs. Extrinsic allergic alveolitis is not limited to Aspergillus or even fungal spores, but is caused by the inhalation of antigenic dusts. These dusts are rarely if ever composed of one organic substance but tend to be a variable mixture of fungal and actinomycete spores, animal proteins and other organic matter. 'Occupational mycoses' are forms of extrinsic allergic alveolitis They are all inflammatory reactions caused by breathing high concentrations of mould spores and other antigenic organic matter. Some forms of these illdefined human diseases have been associated particularly with exposure to high concentrations of Aspergillus spores, including farmer's lung, malt worker's lung, compost lung and bird fancier's lung. Malt worker's lung, one of the best known of these, is an occupational mycosis encountered during beer manufacture correlated with inhalation of high concentrations of Aspergillus clavatus and A. fumigatus spores from contaminated barley.

Adapted from An Overview of the Genus Aspergillus by Joan W. Bennett writing in Aspergillus: Molecular Biology and Genomics

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Aspergillus food fermentations

Food fermentations are ancient technologies that harness microorganisms and their enzymes to improve the human diet. Fermented foods keep better, have enhanced flavours, textures and aromas, and may also possess certain health benefits including superior digestibility. For Buddhists and other vegetarians, fermented foods serve as palatable, protein-rich meat substitutes. Suggested reading: Probiotics Publications

Asian cuisines rely on a large repertoire of fermented foods. In particular, Aspergillus oryzae and A. sojae, sometimes called koji moulds, are employed in many ways. Their hydrolytic enzymes suit them for growth on starch and other carbohydrate-rich substrates. In the koji process, fungal enzymes perform the same function as the malting enzymes used in the beer fermentations of western cultures. The koji moulds release amylases that break down rice starch which in turn can be fermented to make rice wine. Fermented rice beverages have numerous local variations and names depending on country and region. Rice wine is called shaoshing in parts of China, sake in Japan, takj or yakju in Korea, as well as by many other names across Asia.
The koji moulds are also effective in a variety of legume fermentations of which miso and soy sauce are best known. Miso is a mixture of soybeans and cereals usually used to flavour soups. Soy sauce is a flavourful, salty liquid sauce made from soybeans that have been fermented by koji moulds, yeasts, as well as several halophilic bacteria. Other names for soy sauce include jiangyou (China), makjang and kaniang (Korea), toyo (Philippines) and siiu (Thailand). Suggested reading: Probiotics Publications

The first patent on a purified microbial enzyme was awarded in 1894. Companies were established in New Jersey and New York to produce bulk enzymes from Aspergillus and other microbes. Modern commercial enzymology is a thriving bio-based business in which A. niger and A. oryzae are among the major producers for hydrolytic enzymes. As high capacity secretors, their extracellular enzymes easily can be exploited for the production of enzymes used in the baking, beverage and brewing industries; in making animals feeds; and in the paper pulping industry. A. niger has been developed as an efficient host for the production of heterologous proteins using genetic engineering techniques. A. oryzae also has been extensively engineered.

New and more extensive uses for fungal enzymes are envisioned in contemporary biotechnology because experts on energy policy are focusing on 'green' methods of biomass transformation. Plant-derived biomass theoretically could replace petrochemical feedstocks for certain chemical processes. Moulds have numerous enzymes that can turn complex polymers into sugars, lipids and other simpler molecules that can be used for fuels and chemical synthesis. Although much of the research has focused on the genus Trichoderma, Aspergillus represents a huge potential for finding new enzymes that could be used to convert plant biomass into fuels and other industrially useful products.

Adapted from An Overview of the Genus Aspergillus by Joan W. Bennett writing in Aspergillus: Molecular Biology and Genomics

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Aspergillus biotechnology

Species within the genus Aspergillus have a large chemical repertoire. Commodity products produced in Aspergillus cell 'factories' include citric, gluconic, itaconic and kojic acid. The use of Aspergillus niger in citric acid production dates back to 1917. Citric acid is one of the most widely used food ingredients. It also has found use in the pharmaceutical and cosmetic industries as an acidulant and for aiding in the dissolution of active ingredients. Other technical applications of citric acid are as a hardener in adhesive and for retarding the setting of concrete. Citric acid is a true 'bulk chemical' with an estimated production approximating more than 1.6 billion kg each year A. niger also has found use in the industrial production of gluconic acid, which is used as an additive in certain metal cleaning applications, as well as for the therapy for calcium and iron deficiencies. Aspergillus terreus is used for itaconic acid production, a synthetic polymer. A. oryzae is fermented for kojic acid production which is used for skin whitening and as a precursor for synthesis of flavour enhancers. Suggested reading: Microbial Production of Biopolymers

Several Aspergillus secondary metabolites also have major economic importance of which the statins and their derivatives are most profitable. These cholesterol lowering drugs are now among the mostly widely used medicines. The first statin, mevastatin from Penicillium citrinum, was discovered in Japan. The first statin approved for human use, lovastatin, is a secondary metabolite isolated from Aspergillus terreus. Lovastatin was sold under the brand named MevacorTM. The statins are merely one family of useful, biologically-active secondary metabolites isolated from Aspergillus. Other compounds with pharmacological activities include cholecystokinin and neurokinin antagonists, ion channel ligands, antifungal drugs and a host of other compounds.

Adapted from An Overview of the Genus Aspergillus by Joan W. Bennett writing in Aspergillus: Molecular Biology and Genomics

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Aspergillus taxonomy

The genus Aspergillus poses taxonomic problems for identification, nomenclature, and classification. Suggested reading: Aspergillus: Molecular Biology and Genomics

Identification and intrageneric categories

The defining characteristic of the genus Aspergillus is the aspergillum-like spore-bearing structure. It is the most important microscopic character used in Aspergillus taxonomy. During mycelial differentiation certain cells enlarge, develop a heavy cell wall and form 'T' or 'L' shaped 'foot cells' (which are not separate cells) that produce a single conidiophore perpendicular to the long axis of the cell. Sometimes it is difficult to see the foot 'cell,' but when visible, morphologists take it as strong evidence that an isolate is an Aspergillus species. The erect hyphal branch developing from the foot cell is the conidiophore, which enlarges at its apex to form a rounded, elliptical or club shaped vesicle. The fertile area of the vesicle gives rise to a layer of cells called phialides (or steigmata in the older literature) that produce long chains of mitotic spores called conidia or conidiospores. The size and arrangement of the conidial heads as well as the colour of the spores they bear are important identifying characteristics. For example, species in the A. niger group bear black spores, the A. ochraceus group is yellow to brown, while
A. fumigatus, A. nidulans, and A. flavus are green.

The major cultural features used in species identification are the colour of the colony, the growth rate and thermotolerance. Aspergilli have varying morphological and growth response to different nutrients so it is important to standardize conditions. Species identification depends upon pure cultures grown on known media. The early taxonomic micrographs used a defined medium often called 'Czapek-Dox medium' which contains sucrose as the carbon source and nitrate as the nitrogen source. Strain variation is quite extensive within species and a variety of subtle effects such as air exchange, light and volume of the medium can affect morphology. Contemporary taxonomists usually grow strains on several media, at several temperatures, to identify species.

In addition to the conidiophore, other morphological structures useful for identification include cleistothecia, Hülle cells and sclerotia. Both cleistothecia and sclerotia are closed and usually round structures about the size of a poppy seed that may be so abundant as to dominate a colony. Cleistothecia are the sexual reproductive stage and contain the meiotic ascospores borne within asci. In some of the early monographs cleistothecia are called perithecia; this latter term is now limited to ascus-bearing bodies that are open at one end such as those produced by Neurospora crassa. Hülle cells are thickened, often globose, cells that are associated with cleistothecia. Sclerotia are rounded masses of mycelium with an outer melanized rind that macroscopically resemble cleistothecia but do not contain sexual spores. They are believed to serve as resting structures that allow species to survive adverse growth conditions. Finally, some taxonomists supplement these major characters with biochemical characteristics such as secondary metabolite production or ultramicroscopic traits such as spore ornamentation.

During the 20th century, as mycologists isolated and identified increasing numbers of isolates, the number of named species of Aspergillus increased. These tended to fall into morphologically distinct clusters so in order to facilitate identification the genus was divided into intrageneric 'groups'. For example, the Aspergillus glaucus group was characterized by abundant, typically green conidial heads, with perithecia (sic) generally present while the Aspergillus ochraceous group had yellow conidia and abundant cream to purplish-coloured sclerotia. Unfortunately, the term 'group' does not have nomenclatural status within the formal rules of biological nomenclature. The genus was reorganized into a new subgeneric taxonomic hierarchy based on 'sections.' In this system, the subgenus 'Aspergillus' consists of xerophilic species. A. glaucus is the type species, classified in the subgenus Aspergillus and the section Aspergillus. A new subgenus was introduced called Circumdata that encompassed seven sections, in which 'section circumdati' was the new rubric for the old 'A. ochraceous group'. The attempted imposition of subgeneric epithets, only one of which is called 'Aspergillus' is extremely confusing and has not caught on. On the other hand, most taxonomists now use the term 'section' rather than 'group' for Aspergillus intrageneric classifications and identifications.

Nomenclature

Moulds that produce a characteristic asexual spore head that looks like an aspergillum are placed together in the genus Aspergillus. There are approximately 250 named species of Aspergillus. This number is likely to increase significantly in the near future because of increasing application of the phylogenetic species concept based on DNA sequence data rather than on visible morphological characters. Many Aspergillus species and strains have industrial importance, so the delineation of species in this genus is frequently a matter of contention in the patent world. The widespread acceptance of 'phylogenetic species' undoubtedly will have future legal ramifications.

In 1854, early in the scientific history of this genus, deBary became the first person to notice that an Aspergillus mycelium could produce a cleistothecium as well as an aspergillum. DeBary's observation was significant because the cleistothecium-producing mould had been observed before and given its own name: Eurotium herborarium. When DeBary realized that A. glaucum and E. herborarium were different reproductive phases of the same organism, it was an important milestone in mycology and also the beginning of a nomenclatural predicament that persists until this day. Since deBary's original observation, many other fungal species both within and without the genus Aspergillus have been named on the basis of their asexual stage and then 'connected' ('linked') to a sexual stage with a different genus and species name. Which name should be used? Early taxonomists concluded that both names were valid and instituted a system of dual naming.

With the exception of fossils, fungi are the only organisms that depart from one of the basic rules of biological nomenclature, i.e. that each taxonomic group can bear only one correct name. Since 1905, the Botanical Code (which governs the naming of plants and fungi) has allowed two different names to be applied to the same organism, depending on whether it is viewed in its sexual or asexual stage. Under this system of taxonomic governance, Article 59 permits dual nomenclature. When a sexual phase is known, the name for this phase takes precedence. According to these rules, Aspergillus nidulans, the well known genetic model, should be called Emericella nidulans. Indeed, it is indexed as such within GenBank. However, most popular and professional usage continues to call it Aspergillus. A Google search under the entry 'Aspergillus nidulans' yielded 725,000 hits while 'Emericella nidulans' gave fewer than 60,000, a difference of more than an order of magnitude.

Some Aspergillus species regularly produce both sexual and asexual spores; in other species the sexual form is rare; for still others, sexual spores have never been seen - and perhaps never will be seen. The names used for currently accepted sexual genera with close phylogenetic relationship or known linkage to Aspergillus species (representative Aspergillus species given in parenthesis) are: Chaetosartorya (A. wentii); Emericella (A. nidulans); Eurotium (A. glaucus); Fennellia (A. terreus); Hemicarpenteles (A. paradoxus); Neocarpenteles (A. clavatus); Neosartorya (A. fumigatus); Petromyces (A. flavus and possibly A. niger); Sclerocleista (A. ornatus); and Warcupiella (A. spinnulosus). Rigid interpreters of nomenclatural rules believe that it is wrong to use the name Aspergillus to denote a fungus with a known sexual stage and that only the generic name associated with the sexual stage should be used. Nevertheless, outside the community of fungal taxonomy and 'strict interpreters' of the Botanical Code, the proliferation of names for a genus that most biologists know as Aspergillus causes bewilderment. Dual nomenclature is also a major problem for information retrieval.

The proliferation of arcane terminology is also problematic. For many years, mycologists called those fungi incapable of forming sexual spores 'imperfect' while the sexual forms were called 'perfect.' Another term often encountered was 'pleomorphic,' referring to that fact that these organisms could take more than one form. ('Pleomorphism' is particularly confusing because it is sometimes used to describe the yeast-mycelial phase transition characteristic of some medically important fungai, a transition that is more properly called 'dimorphism'). When an 'imperfect' fungus also was found to be 'perfect' additional problems of etymology developed surrounding the use of the terms 'asexual phase/stage/state' and 'sexual phase/stage/state.' All of these terms were used inconsistently and interpreted differently. For this reason, during the late 1970s, a new set of terminology was introduced whereby anamorph refers to the asexual, mitotic-spore-bearing morphological phase; teleomorph refers to the sexual meiotic-spore-bearing morphological phase; while holomorph refers to the 'whole fungus'. In 1981, this terminology was accepted by the Botanical Congress. Both 'anamorph' and 'teleomorph' have gained widespread acceptance; however, 'holomorph' has had less linguistic success.

In summary, many Aspergillus species have two names, an exception to most rules of scientific nomenclature that is nevertheless legal under the Botanical Code. This mycological exceptionalism has caused regular and heated debates ever since the Botanical Code was formulated. Different generations of taxonomists have revised the rules pertaining to fungal nomenclature as better data have come along that inform our understanding of fungal speciation. These revisions will continue to be made into the foreseeable future. Nevertheless, there are experts who seem to forget that rigid rules and neat categories don't always mesh with the variability of living systems and the realities of human language usage. Sometimes nomenclatural decisions go against common sense. One rationale for biological nomenclature is to provide stability. Another is to aid communication. Proliferation of jargon and frequent changes of specific and generic epithets do neither.

Suprageneric classification

Aspergillus presents several classification difficulties that are intertwined with its nomenclatural intricacies. A form taxon (pl. form taxa) is a group, used for convenience, whose evolutionary and other relationships are not known. Form genera are used in classifying fossil plants, but they also have had widespread application in the history of Aspergillus classification. For a long time, all asexual (anamorphic) fungal species were classified into a form group commonly called the 'fungi imperfecti' or, more technically, Fungi Imperfecti. Depending on the author, the group was ranked as a class (Deuteromycetes) or a subdivision/subphylum (Deuteromycotina). The fungi imperfecti sometimes were subdivided into form classes in which the moulds were grouped together as Hypomycetes. These 'artificial' rubrics were used to encompass asexual groups, while other higher order 'natural' categories were used to categorize species that produce by sexual means. Since all taxonomic classification schemes are human constructs designed to catalogue living things, many philosophical and practical objections are inherent in the concept of 'natural categories.

Nevertheless, modern taxonomists seek a more 'natural' classification scheme based on evolutionary criteria. Such phylogenetic classifications seem more possible now that traditional morphological markers have been supplemented with nucleic acid sequences. In particular, DNA markers such as ITS regions or conserved genes such as calmodulin, tubulin or RNA polymerase are used to conduct molecular phylogenetic studies. Species with few nucleotide differences are considered more closely related than those with many. Taxonomists compare the sequence differences between species and use computer programs to come up with a hierarchy of evolutionary relationships. Despite the fact that such gene trees - especially those based on single genes - are error prone, despite the fact that different genes evolve at different rates, and despite the fact that horizontal gene transfer can muddy phylogenetic analysis, such analyses are largely robust and have revolutionized all taxonomic systems. It now seems likely that the aspergilli are all descended from one common ancestor, i.e. they constitute a monophyletic group. It is believed that that the ancestral form was sexually producing and that independent losses of sexual reproduction occurred repeatedly.

These molecular phylogenetic analyses have ramifications for both classification and nomenclature. It can be assumed that fungi called Aspergillus are descended from the same ancestral groups as their named teleomorphs. From the perspective of classification, it means that the old form taxa categories, (i.e. the fungi imperfecti and the Deuteromycotina) can be retired. In theory, mycologists have done so and these taxa are no longer formally accepted. Aspergillus species now are classified firmly within the Ascomycota. However, in practice the old terms for form taxa are still widely used and applied. At the time of this writing, a Google search revealed 122,000 hits for 'fungi imperfecti' and 87,500 for 'Deuteromycotina'.

The clear placement of all Aspergillus species within the Ascomycete lineage, along with the 10 named Aspergillus teleomorphs, has led some taxonomists to suggest that they all could be placed within a teleomorphic nomenclatural system, even without any sexual structure having been found. Nonetheless, the question remains: Are all Aspergillus species anamorphs of some kind of ascomycete? Should anamorphic Aspergillus species be classified within, and named for, a teleomorphic genus based on DNA evidence even when they lack a known teleomorph? These questions raise both theoretical and practical issues. Suppose the teleomorph does not exist? Suppose some large and successful groups of aspergilli have evolved a purely clonal and asexual form of reproduction? Does it make sense to rename them based on a morphological structure they do not possess? Caution and conservatism counsel the retention of both dual
nomenclature and the genus name Aspergillus.

Commentary on taxonomy

Living things evolve. Natural systems are messy. Groups of closely related organisms do not always lend themselves to tidy classification schemes. The human need for neat categories coupled with an unfortunate tendency on the part of some scientists to view the Botanical Code as 'etched in stone,' means that over zealous interpretations of the Botanical Code can trump reasonableness and practicality. The Code is authored by human beings and necessarily is open to changes as new discoveries are made. For the sake of stability, these changes are made slowly and usually after considerable debate within the scientific community. Nonetheless it is important to remember that the debate mostly occurs between a relatively small number of people who are involved in policing the fine points of biological nomenclature. Even among this small group, it is not always easy to gain consensus. For example, when a assemblage of prominent mycologists gathered at an important meeting held in Newport, Oregon, in 1992, they discussed the provisions of Article 59 in detail. At the end of the discussion, 19 people voted to retain the dual system; 17 wanted to integrate mitotic and meiotic fungi into the same genera, and only five would accept the use of the teleomorph name for both morphs. Similarly, in 2007, an international workshop with 39 experts was held in Utrecht, the Netherlands on 'Aspergillus systematics in the genomics era.' In the light of the overwhelming molecular data placing Aspergillus among the Ascomycetes, the question of dual nomenclature was revisited. In the final vote, the majority of participants decided that it was best to retain dual names 'where necessary'. It is likely that naming and classifying Aspergillus species - and many other anamorphic fungi - will remain a contentious area within mycology for the foreseeable future. Suggested reading: Fungal Publications

Adapted from An Overview of the Genus Aspergillus by Joan W. Bennett writing in Aspergillus: Molecular Biology and Genomics

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Physiology and ecology of Aspergillus

Aspergillus spores are common components of aerosols where they drift on air currents, dispersing themselves both short and long distances depending on environmental conditions. When the spores come in contact with a solid or liquid surface, they are deposited and if conditions of moisture are right, they germinate. The ability to disperse globally in air currents and to grow almost anywhere when appropriate food and water are available means that 'ubiquitous' is among the most common adjectives used to describe these moulds.

One of the defining characteristics of the entire fungal kingdom is its distinctive nutritional strategy. These organisms secrete acids and enzymes into the surrounding environment, breaking down polymeric molecules down into simpler ones that are then absorbed back into the fungal cell. Fungi, like animals, are heterotrophic. While animals eat their food and then digest it, fungi first digest their food and then 'eat' it. Gaining access to nutrients is aided by mechanical forces whereby fungal hyphal tips grow into and through their food substrates. Species of Aspergillus are typical examples of the fungal life style. They are most often found in terrestrial habitats and are commonly isolated from soil and associated plant litter. The decomposition process carried out by these moulds is important in driving natural cycling of chemical elements, particularly in the carbon cycle where they contribute to replenishment of the supply of carbon dioxide and other inorganic compounds.

In the ecosystem, different substrates are attacked at different rates by consortia of organisms from different kingdoms. Aspergillus and other moulds play an important role in these consortia because they are adept at recycling starches, hemicelluloses, celluloses, pectins and other sugar polymers. Some aspergilli are capable of degrading more refractory compounds such as fats, oils, chitin, and keratin. Maximum decomposition occurs when there is sufficient nitrogen, phosphorus and other essential inorganic nutrients. Fungi also provide food for many soil organisms.

For Aspergillus the process of degradation is the means of obtaining nutrients. When these moulds degrade human-made substrates, the process usually is called biodeterioration. Both paper and textiles (cotton, jute, and linen) are particularly vulnerable to Aspergillus degradation. Our artistic heritage is also subject to Aspergillus assault. To give but one example, after Florence in Italy flooded in 1969, 74% of the isolates from a damaged Ghirlandaio fresco in the Ognissanti church were Aspergillus versicolor. Suggested reading: Microbial Biodegradation: Genomics and Molecular Biology

Similarly, foods utilized by humans and our domestic animals are good nutritional sources for Aspergillus. Words like 'decay,' 'rot' and 'spoilage' are used to describe such fungal utilization of our foodstuffs, which can occur in the field prior to harvest, during storage, and after commercial processing or cooking in the home. Although foods with an acidic pH, dried foods, and those with a high concentration of sugars such as jams and jellies normally do not support microbial growth many members of the A. glaucus group (Eurotium) are able to grow at low water activity. These species even have been isolated from salted, dry fish. In the same way, grains, nuts and spices, all of which have relatively low amounts of water, regularly are attacked by moderately xerophilic species of Aspergillus. Suggested reading: Foodborne Pathogens: Microbiology and Molecular Biology

Adapted from An Overview of the Genus Aspergillus by Joan W. Bennett writing in Aspergillus: Molecular Biology and Genomics

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Introduction to Aspergillus

Aspergillus is one of the oldest named genera of fungi. By 1926, Aspergillus had become one of the best-known and most studied mould groups. Their prevalence in the natural environment, their ease of cultivation on laboratory media and the economic importance of several of its species ensured that many mycologists and industrial microbiologists were attracted to their study. Aspergilli grow abundantly as saprophytes on decaying vegetation and have been found in large numbers in mouldy hay, organic compost piles, leaf litter and the like. Most species are adapted for the degradation of complex plant polymers, but they can also dine on substrates as diverse as dung, human tissues, and antique parchment. There is even a report of an unidentified Aspergillus species being capable of the solubilization of low rank coal. Suggested reading: Aspergillus: Molecular Biology and Genomics

This common mould is involved in many industrial processes including enzymes (e.g. amylases), commodity chemicals (e.g. citric acid) and food stuffs (e.g. soy sauce). In classical fungal genetics, one species Aspergillus (Emericella) nidulans has been used to elucidate the parasexual cycle, as well as to understand basic concepts in regulation of metabolic pathways, the cell cycle, intron splicing and hyphal polarity. Several species contaminate grains and other foods with toxic metabolites that are a threat to the health of humans and other animals. Certain Aspergillus species also can infect humans directly causing both localized and systemic infections, especially in immunocompromised individuals. Suggested reading: Fungal Publications

Adapted from An Overview of the Genus Aspergillus by Joan W. Bennett writing in Aspergillus: Molecular Biology and Genomics

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An Overview of the Genus Aspergillus

Aspergillus is the name used for a genus of moulds that reproduce only by asexual means. The mor­phology of the conidiophore, the structure that bears asexual spores, is the most important taxo­nomic character used in Aspergillus taxonomy. Aspergillus species are common and widespread. They are among the most successful groups of moulds with important roles in natural ecosys­tems and the human economy.
Among scientists working on Aspergillus, there is a continuing fascination with their bio­technological potential. In addition to producing numerous useful extracellular enzymes and or­ganic acids, these moulds also produce secondary metabolites of importance in biotechnology.

Some Aspergillus species function as plant and/or animal pathogens. Aspergillosis is the name given to all animal diseases caused by growth of any member of the genus on a liv­ing host. Immunosuppression is generally a prerequisite for systemic Aspergillus infections in humans. The incidence of systemic aspergillosis, the most serious form, is on the rise and imposes an increasing medical burden upon hospitals and physicians. Better antifungal drugs and diagnostic methods are needed.

Advances in Aspergillus genomics are giving us new tools for understanding this extremely di­verse genus. Hitherto undiscovered sexual stages have been discovered based on findings from genomics. Molecular biologists are trying to un­derstand the mechanisms by which pathogenic­ity and sexuality work and to deconstruct the physiological pathways that are central to these processes. Evolutionary biologists are focusing on the forces that drive variation within and among population. Economically important species are being re-tested for new capabilities using new screens developed with the aid of post genomic technologies.

Adapted from An Overview of the Genus Aspergillus by Joan W. Bennett writing in Aspergillus: Molecular Biology and Genomics

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