Central Carbon Metabolic Pathways in Streptomyces
Central Carbon Metabolic Pathways in Streptomyces
from Geertje van Keulen, Jeroen Siebring and Lubbert Dijkhuizen writing in Streptomyces: Molecular Biology and Biotechnology:
Streptomyces and other actinomycetes are fascinating soil bacteria of major economic importance. They produce 70% of antibiotics known to man and numerous other pharmaceuticals for treatment of, e.g. cancer, a range of infections, high cholesterol, or have immunosuppressive activity. It is not surprising that the multitude of gene clusters encoding for the biosynthesis of known and unknown secondary metabolites in genome sequences of a wide range of actinomycetes have received much attention in the last few years. In contrast, there is much less understanding of primary metabolism and its control in actinomycetes, despite its importance as supply pathways of precursors for secondary metabolite production. Streptomyces: Molecular Biology and Biotechnology describes current information on the central carbon metabolic pathways in streptomycetes, focussing on glycolysis, pentose phosphate pathway, Entner-Doudoroff pathway, gluconeogenesis, and the source of phosphate for phosphorylation reactions. In addition, recent developments providing a greater insight into links with secondary metabolism in Streptomyces are reviewed.
Further reading: Streptomyces: Molecular Biology and Biotechnology
from Geertje van Keulen, Jeroen Siebring and Lubbert Dijkhuizen writing in Streptomyces: Molecular Biology and Biotechnology:
Streptomyces and other actinomycetes are fascinating soil bacteria of major economic importance. They produce 70% of antibiotics known to man and numerous other pharmaceuticals for treatment of, e.g. cancer, a range of infections, high cholesterol, or have immunosuppressive activity. It is not surprising that the multitude of gene clusters encoding for the biosynthesis of known and unknown secondary metabolites in genome sequences of a wide range of actinomycetes have received much attention in the last few years. In contrast, there is much less understanding of primary metabolism and its control in actinomycetes, despite its importance as supply pathways of precursors for secondary metabolite production. Streptomyces: Molecular Biology and Biotechnology describes current information on the central carbon metabolic pathways in streptomycetes, focussing on glycolysis, pentose phosphate pathway, Entner-Doudoroff pathway, gluconeogenesis, and the source of phosphate for phosphorylation reactions. In addition, recent developments providing a greater insight into links with secondary metabolism in Streptomyces are reviewed.
Further reading: Streptomyces: Molecular Biology and Biotechnology
Protein Secretion in Streptomyces
Protein Secretion in Streptomyces
from Tracy Palmer and Matthew I. Hutchings writing in Streptomyces: Molecular Biology and Biotechnology:
The saprophytic lifestyle of Streptomyces requires them to secrete prolific numbers of proteins. For example, inspection of the genome sequence of Streptomyces coelicolor indicates it encodes some 819 proteins with predicted signal peptides. This represents more than 10% of the protein coding genes and is most likely an underestimate. Many secreted proteins are required for nutrient capture, and there is an abundance of secreted hydrolases for the breakdown of complex carbohydrates (including cellulose and chitin), peptides and phospho-compounds. In addition to proteins that are secreted into the milieu, many proteins are covalently anchored to the cell surface by means of either a lipid anchor to the membrane or by covalent attachment to the cell wall through the sortase system. Here we summarise what is known about the different protein secretion systems utilised by Streptomyces, and the mechanisms by which proteins are anchored to the extracellular surface.
Further reading: Streptomyces: Molecular Biology and Biotechnology
from Tracy Palmer and Matthew I. Hutchings writing in Streptomyces: Molecular Biology and Biotechnology:
The saprophytic lifestyle of Streptomyces requires them to secrete prolific numbers of proteins. For example, inspection of the genome sequence of Streptomyces coelicolor indicates it encodes some 819 proteins with predicted signal peptides. This represents more than 10% of the protein coding genes and is most likely an underestimate. Many secreted proteins are required for nutrient capture, and there is an abundance of secreted hydrolases for the breakdown of complex carbohydrates (including cellulose and chitin), peptides and phospho-compounds. In addition to proteins that are secreted into the milieu, many proteins are covalently anchored to the cell surface by means of either a lipid anchor to the membrane or by covalent attachment to the cell wall through the sortase system. Here we summarise what is known about the different protein secretion systems utilised by Streptomyces, and the mechanisms by which proteins are anchored to the extracellular surface.
Further reading: Streptomyces: Molecular Biology and Biotechnology
Differentiation in Streptomyces
Differentiation in Streptomyces: The Properties and Programming of Diverse Cell-types
from Keith F. Chater writing in Streptomyces: Molecular Biology and Biotechnology:
Streptomyces colonies are complex differentiated organisms, generated from a single ovoid spore by filamentous growth and branching. Eventually, much of this biomass is converted to large numbers of spores in long chains on specialised aerial hyphae. During colony development, different cellular compartments have different physiology and metabolism, and exoskeletal and cytoskeletal elements bring about different morphological changes. These cellular differentiating processes are underpinned by a large number of regulatory genes, often operating in cascades. During the transition from biomass accumulation to reproductive development, antibiotics are made, sometimes under the control of developmental regulators.
Further reading: Streptomyces: Molecular Biology and Biotechnology
from Keith F. Chater writing in Streptomyces: Molecular Biology and Biotechnology:
Streptomyces colonies are complex differentiated organisms, generated from a single ovoid spore by filamentous growth and branching. Eventually, much of this biomass is converted to large numbers of spores in long chains on specialised aerial hyphae. During colony development, different cellular compartments have different physiology and metabolism, and exoskeletal and cytoskeletal elements bring about different morphological changes. These cellular differentiating processes are underpinned by a large number of regulatory genes, often operating in cascades. During the transition from biomass accumulation to reproductive development, antibiotics are made, sometimes under the control of developmental regulators.
Further reading: Streptomyces: Molecular Biology and Biotechnology
Streptomyces Conjugative Genetic Elements
Streptomyces Conjugative Genetic Elements
from Jutta Vogelmann, Wolfgang Wohlleben and Günther Muth writing in Streptomyces: Molecular Biology and Biotechnology:
Antibiotic producing actinomycetes contain a huge variety of different plasmids, distinguished in size, topology, replication mechanism and copy number. Some are able to integrate into the chromosome by site specific recombination. With the exception of the huge linear plasmids, Streptomyces plasmids encode only functions involved in replication, stable maintenance and conjugative transfer. The Streptomyces conjugation system is unique, requiring a single plasmid-encoded protein, TraB. TraB is a hexameric ring ATPase with similarity to the septal DNA translocator proteins FtsK/SpoIIIE which are involved in chromosome segregation during cell division and sporulation. TraB binds non-covalently to 8bp TRS repeats present in the clt locus and transfers double stranded plasmid DNA from the donor to the recipient. Presence of clt-like sequences in the chromosome of S. coelicolor suggests that chromosomal genes are mobilized independently from the plasmid. Following primary transfer from the donor into the recipient, the plasmid is translocated via septal crosswalls resulting in intramycelial plasmid spreading. Plasmid spreading involves five to seven plasmid-encoded Spd-proteins. Protein-protein interaction studies with Spd-proteins of the conjugative plasmid pSVH1 suggest formation of a large DNA-translocation apparatus. One component, the integral membrane protein SpdB2 was shown to form pore structures in lipid bilayers.
Further reading: Streptomyces: Molecular Biology and Biotechnology
from Jutta Vogelmann, Wolfgang Wohlleben and Günther Muth writing in Streptomyces: Molecular Biology and Biotechnology:
Antibiotic producing actinomycetes contain a huge variety of different plasmids, distinguished in size, topology, replication mechanism and copy number. Some are able to integrate into the chromosome by site specific recombination. With the exception of the huge linear plasmids, Streptomyces plasmids encode only functions involved in replication, stable maintenance and conjugative transfer. The Streptomyces conjugation system is unique, requiring a single plasmid-encoded protein, TraB. TraB is a hexameric ring ATPase with similarity to the septal DNA translocator proteins FtsK/SpoIIIE which are involved in chromosome segregation during cell division and sporulation. TraB binds non-covalently to 8bp TRS repeats present in the clt locus and transfers double stranded plasmid DNA from the donor to the recipient. Presence of clt-like sequences in the chromosome of S. coelicolor suggests that chromosomal genes are mobilized independently from the plasmid. Following primary transfer from the donor into the recipient, the plasmid is translocated via septal crosswalls resulting in intramycelial plasmid spreading. Plasmid spreading involves five to seven plasmid-encoded Spd-proteins. Protein-protein interaction studies with Spd-proteins of the conjugative plasmid pSVH1 suggest formation of a large DNA-translocation apparatus. One component, the integral membrane protein SpdB2 was shown to form pore structures in lipid bilayers.
Further reading: Streptomyces: Molecular Biology and Biotechnology
Streptomyces Genome
Genome Architecture
from Ralph Kirby and Carton W. Chen writing in Streptomyces: Molecular Biology and Biotechnology
Linear replicons are relatively uncommon among bacteria and their preponderance among the Actinomycetales, and within the Streptomyces in particular, poses some interesting questions. These novel bacterial replicons are capped by terminal proteins that are covalently bound to the 5' ends of the linear DNA and these terminal structures are directly involved in replicating and protecting the ends of the linear genome. In addition and perhaps related to their linear nature, these genomes are among the largest bacterial chromosomes. As far as can be ascertained at present, these large genomes have a specific organizational structure in terms of their genes. The genome structure can be divided into a core region that is present syntenously in most Actinomycetales, two terminal regions that are highly variable throughout the explored Streptomyces and two regions to the left and right of the core region that contain many syntenous genes specific to the Streptomyces and not found in other Actinomycetales. Genome dynamics seems to be important to the Streptomyces with plasmid-chromosome interactions, horizontal gene transfer and interspecific recombination probably playing important roles in how these genomes to adapt to the diverse environment they reside in. Exploring the genome architecture of the Streptomyces helps our understanding of how and why the genus Streptomyces has a unique place in the evolution of the bacteria.
Further reading: Streptomyces: Molecular Biology and Biotechnology
from Ralph Kirby and Carton W. Chen writing in Streptomyces: Molecular Biology and Biotechnology
Linear replicons are relatively uncommon among bacteria and their preponderance among the Actinomycetales, and within the Streptomyces in particular, poses some interesting questions. These novel bacterial replicons are capped by terminal proteins that are covalently bound to the 5' ends of the linear DNA and these terminal structures are directly involved in replicating and protecting the ends of the linear genome. In addition and perhaps related to their linear nature, these genomes are among the largest bacterial chromosomes. As far as can be ascertained at present, these large genomes have a specific organizational structure in terms of their genes. The genome structure can be divided into a core region that is present syntenously in most Actinomycetales, two terminal regions that are highly variable throughout the explored Streptomyces and two regions to the left and right of the core region that contain many syntenous genes specific to the Streptomyces and not found in other Actinomycetales. Genome dynamics seems to be important to the Streptomyces with plasmid-chromosome interactions, horizontal gene transfer and interspecific recombination probably playing important roles in how these genomes to adapt to the diverse environment they reside in. Exploring the genome architecture of the Streptomyces helps our understanding of how and why the genus Streptomyces has a unique place in the evolution of the bacteria.
Further reading: Streptomyces: Molecular Biology and Biotechnology
Neisseria book review
I am pleased to provide the following excerpt from a book review of Neisseria: Molecular Mechanisms of Pathogenesis:
"an excellent, comprehensive and updated review ... The editors, both experienced in the Neisseria field, have recruited 43 contributors from five different countries. Many of these individuals are well-recognized experts, front-line researchers and/or key opinion leaders in their topics. They provide, evaluate and discuss detailed up-to-date understanding, the significance of different findings, theories, hypotheses and conclusions, and future directions in a research, clinical and public health perspective. The volume is valuable and timely ... Most chapters ... are excellent, comprehensive, important, updated, well-written, and contain many relevant references and informative figures/tables summarizing the key information ... the 'future trends' are valuably emphasized in most chapters. Some chapters even recommend good web resources for further reading ... the editors of the present volume have collated an impressive group of well-recognized experts that provide exceedingly interesting, comprehensive and up-to-date understanding regarding molecular mechanisms of pathogenesis in Neisseria, as well as an excellent bibliography for further reading. The volume is valuable, timely and can be highly recommended for researchers, microbiologists, molecular biologists, epidemiologists, clinicians, vaccine manufacturers and students, who are involved and/ or interested in any topic involving pathogenic Neisseria species." from Magnus Unemo (Orebro, Sweden) writing in Expert Rev. Anti Infect. Ther. (2010) 8: 871–875. read more ...
"an excellent, comprehensive and updated review ... The editors, both experienced in the Neisseria field, have recruited 43 contributors from five different countries. Many of these individuals are well-recognized experts, front-line researchers and/or key opinion leaders in their topics. They provide, evaluate and discuss detailed up-to-date understanding, the significance of different findings, theories, hypotheses and conclusions, and future directions in a research, clinical and public health perspective. The volume is valuable and timely ... Most chapters ... are excellent, comprehensive, important, updated, well-written, and contain many relevant references and informative figures/tables summarizing the key information ... the 'future trends' are valuably emphasized in most chapters. Some chapters even recommend good web resources for further reading ... the editors of the present volume have collated an impressive group of well-recognized experts that provide exceedingly interesting, comprehensive and up-to-date understanding regarding molecular mechanisms of pathogenesis in Neisseria, as well as an excellent bibliography for further reading. The volume is valuable, timely and can be highly recommended for researchers, microbiologists, molecular biologists, epidemiologists, clinicians, vaccine manufacturers and students, who are involved and/ or interested in any topic involving pathogenic Neisseria species." from Magnus Unemo (Orebro, Sweden) writing in Expert Rev. Anti Infect. Ther. (2010) 8: 871–875. read more ...
 | Edited by: Caroline Genco and Lee Wetzler "excellent, comprehensive ... valuable and timely ... highly recommended" (Expert Rev. Anti Infect. Ther.)ISBN: 978-1-904455-51-6 Publisher: Caister Academic Press Publication Date: January 2010 Cover: hardback |
Iron Uptake Book Available
The new book on Iron Uptake and Homeostasis in Microorganisms edited by Pierre Cornelis and Simon C. Andrews has been published read more ...
read more ...
 | Edited by: Pierre Cornelis and Simon C. Andrews ISBN: 978-1-904455-65-3 Publisher: Caister Academic Press Publication Date: June 2010 Cover: hardback |
Bifidobacteria Book Available
The new book on Bifidobacteria: Genomics and Molecular Aspects edited by Baltasar Mayo and Douwe van Sinderen has been published read more ...
read more ...
 | Edited by: Baltasar Mayo and Douwe van Sinderen ISBN: 978-1-904455-68-4 Publisher: Caister Academic Press Publication Date: August 2010 Cover: hardback |
Borrelia Book Review
I am pleased to provide the following excerpt from a book review of Borrelia: Molecular Biology, Host Interaction and Pathogenesis:
"This book has 18 chapters and it will cover everything you need to know about these Spirochetes from behaviour in the field to sequencing in a molecular laboratory. Each chapter seems to be written by expert in their Borrelia field and bring updated information about the state-of-art for research of simply general knowledge for this pathogen ... would definitely interest researchers and some teachers seeking research-led examples for their lectures ... this book is a fantastic source of information for scientists working on vector-borne diseases and interested in epidemiology, evolution, genomics ... I truly enjoyed reading this book and would recommend it." from Olivier A E Sparagano (Newcastle University, UK) writing in Parasites and Vectors (2010) 3: 52 read more ...
"This book has 18 chapters and it will cover everything you need to know about these Spirochetes from behaviour in the field to sequencing in a molecular laboratory. Each chapter seems to be written by expert in their Borrelia field and bring updated information about the state-of-art for research of simply general knowledge for this pathogen ... would definitely interest researchers and some teachers seeking research-led examples for their lectures ... this book is a fantastic source of information for scientists working on vector-borne diseases and interested in epidemiology, evolution, genomics ... I truly enjoyed reading this book and would recommend it." from Olivier A E Sparagano (Newcastle University, UK) writing in Parasites and Vectors (2010) 3: 52 read more ...
 | Edited by: D. Scott Samuels and Justin D. Radolf "a fantastic source of information" (Parasites and Vectors)ISBN: 978-1-904455-58-5 Publisher: Caister Academic Press Publication Date: March 2010 Cover: hardback |
Salmonella and Cancer
Salmonella as the paradigm for bacterial therapy of cancer: A progress report
from Robert M. Hoffman writing in Salmonella: From Genome to Function
For over 300 years it has been observed that cancer patients who became infected with bacteria sometimes experienced spontaneous remission of their cancer. Recently, there have been attempts to develop cancer treatments by using tumor-targeting bacteria. Anaerobic microorganisms, such as Clostridium, that preferentially grow in necrotic tumor areas have mostly been used. However, the resulting tumor killing was, at best, limited. Salmonella was originally developed as an antitumor agent by attenuating the bacteria with multiple mutations, including auxotrophs. These multiple auxotrophs appeared to direct the bacteria to the metastatic areas of tumors where more nutrients are available. We have developed a more effective bacterial cancer therapy strategy by targeting viable tumor tissue with Salmonella enterica serovar Typhimurium containing only two auxotrophic mutations. These auxotrophs grow in viable as well as necrotic areas of tumors. However, the auxotrophy severely restricts growth of these bacteria in normal tissue, making this a safe treatment. The S. Typhimurium A1-R mutant, which is auxotrophic for leucine and arginine and had been selected for high antitumor virulence, was effective as monotherapy against human prostate and breast tumors that had been orthotopically implanted in nude mice. The approach described here, where bacterial monotherapy effectively treats primary and metastatic tumors, is a significant improvement over previous bacterial tumor-therapy strategies that require combination with toxic chemotherapy. Exploitation of the tumor-killing capability of Salmonella has great potential for a new paradigm of cancer therapy.
Further reading: Salmonella: From Genome to Function
from Robert M. Hoffman writing in Salmonella: From Genome to Function
For over 300 years it has been observed that cancer patients who became infected with bacteria sometimes experienced spontaneous remission of their cancer. Recently, there have been attempts to develop cancer treatments by using tumor-targeting bacteria. Anaerobic microorganisms, such as Clostridium, that preferentially grow in necrotic tumor areas have mostly been used. However, the resulting tumor killing was, at best, limited. Salmonella was originally developed as an antitumor agent by attenuating the bacteria with multiple mutations, including auxotrophs. These multiple auxotrophs appeared to direct the bacteria to the metastatic areas of tumors where more nutrients are available. We have developed a more effective bacterial cancer therapy strategy by targeting viable tumor tissue with Salmonella enterica serovar Typhimurium containing only two auxotrophic mutations. These auxotrophs grow in viable as well as necrotic areas of tumors. However, the auxotrophy severely restricts growth of these bacteria in normal tissue, making this a safe treatment. The S. Typhimurium A1-R mutant, which is auxotrophic for leucine and arginine and had been selected for high antitumor virulence, was effective as monotherapy against human prostate and breast tumors that had been orthotopically implanted in nude mice. The approach described here, where bacterial monotherapy effectively treats primary and metastatic tumors, is a significant improvement over previous bacterial tumor-therapy strategies that require combination with toxic chemotherapy. Exploitation of the tumor-killing capability of Salmonella has great potential for a new paradigm of cancer therapy.
Further reading: Salmonella: From Genome to Function
Salmonella Biofilms
Salmonella Biofilms: From food to human disease
from Robert W. Crawford, Geoffrey Gonzalez-Escobedo and John S. Gunn writing in Salmonella: From Genome to Function
Bacterial biofilms are increasingly implicated as burdens to food and public safety. Over the past few decades, we have learned that this sessile environment provides diverse species of bacteria selective advantages in natural, medical, and industrial ecosystems, as well as resistance to commonly administered antibiotics and protection from host immune responses during chronic infection of humans and animals. Salmonella spp. are food-borne pathogens that remain a critical health concern in impoverished and industrialized nations. In the laboratory, salmonellae have been shown to form biofilms on a variety of surfaces. These Salmonella spp. biofilms have been found to contaminate plant and animal food sources to cause human disease upon consumption, and/or to enhance salmonellae colonization of and persistence at sites of infection.
Further reading: Salmonella: From Genome to Function
from Robert W. Crawford, Geoffrey Gonzalez-Escobedo and John S. Gunn writing in Salmonella: From Genome to Function
Bacterial biofilms are increasingly implicated as burdens to food and public safety. Over the past few decades, we have learned that this sessile environment provides diverse species of bacteria selective advantages in natural, medical, and industrial ecosystems, as well as resistance to commonly administered antibiotics and protection from host immune responses during chronic infection of humans and animals. Salmonella spp. are food-borne pathogens that remain a critical health concern in impoverished and industrialized nations. In the laboratory, salmonellae have been shown to form biofilms on a variety of surfaces. These Salmonella spp. biofilms have been found to contaminate plant and animal food sources to cause human disease upon consumption, and/or to enhance salmonellae colonization of and persistence at sites of infection.
Further reading: Salmonella: From Genome to Function
Anti-Salmonella immunity
Anti-Salmonella immunity: Highlighting new research in vaccines, mucosal immunology and systemic disease
from Jennifer L. Bishop, Ellen T. Arena, Kenneth W. Harder and B. Brett Finlay writing in Salmonella: From Genome to Function
Enteric fever and non-typhoidal salmonelloses (NTS) are caused by a wide variety of Salmonella enterica serovars and are a serious health threat throughout the world. Immunity to systemic typhoid and NTS requires intricate crosstalk between both innate and adaptive immune cells spanning multiple organ systems. The development of a number of new mouse and in vitro culture models suitable for studying gastroenteritis has highlighted the complexity of mucosal responses and shown how a diverse subset of cells interact within the intestinal architecture to elicit anti-Salmonella immunity. These include specific dendritic cell subsets, natural killer cells and TH17 skewed T helper cells and the repertoire of cytokines they produce, including IL-17, IL-23, IL-22 and IL-15. Furthermore, the importance of commensal microflora has been stressed in various Salmonella models, and new research has shown the various effects of prebiotics, probiotics and antibiotics on Salmonella pathogenesis. Systemic immune responses are also more explicitly understood, as the location and phenotype of cells harboring intracellular bacteria become more defined. A forthcoming book reviews these recent advances and how they are being translated into new therapies and vaccine studies in the human population.
Read more: Salmonella: From Genome to Function
from Jennifer L. Bishop, Ellen T. Arena, Kenneth W. Harder and B. Brett Finlay writing in Salmonella: From Genome to Function
Enteric fever and non-typhoidal salmonelloses (NTS) are caused by a wide variety of Salmonella enterica serovars and are a serious health threat throughout the world. Immunity to systemic typhoid and NTS requires intricate crosstalk between both innate and adaptive immune cells spanning multiple organ systems. The development of a number of new mouse and in vitro culture models suitable for studying gastroenteritis has highlighted the complexity of mucosal responses and shown how a diverse subset of cells interact within the intestinal architecture to elicit anti-Salmonella immunity. These include specific dendritic cell subsets, natural killer cells and TH17 skewed T helper cells and the repertoire of cytokines they produce, including IL-17, IL-23, IL-22 and IL-15. Furthermore, the importance of commensal microflora has been stressed in various Salmonella models, and new research has shown the various effects of prebiotics, probiotics and antibiotics on Salmonella pathogenesis. Systemic immune responses are also more explicitly understood, as the location and phenotype of cells harboring intracellular bacteria become more defined. A forthcoming book reviews these recent advances and how they are being translated into new therapies and vaccine studies in the human population.
Read more: Salmonella: From Genome to Function
The Intracellular lifestyle of Salmonella
The intracellular lifestyle of Salmonella enterica and novel approaches to understand the adaptation to life within the Salmonella-containing vacuole
from Roopa Rajashekar and Michael Hensel writing in Salmonella: From Genome to Function
Salmonella enterica is a facultative intracellular pathogen that resides in a unique membrane-bound compartment, referred to as Salmonella-containing vacuole or SCV. Within the SCV, Salmonella is able to survive the antimicrobial activities of phagocytic cells and can rapidly multiply in a variety of host cells. Intracellular life of Salmonella is dependent on a large number of virulence traits, but the function of the type III secretion system (T3SS) encoded by Salmonella Pathogenicity Island 2 (SPI2) is of central importance. Although more than 20 effector proteins have been identified as translocated by the SPI2-T3SS, the molecular function and contribution to intracellular live is only known for a few of these proteins. Intracellular Salmonella modify basic functions of the host cell such as the structure of the microtubule cytoskeleton and induce a massive reorganization of vesicular transport and the endosomal system. Unique phenomena are the SPI2-dependent induction of extensive tubular membrane aggregations of endosomal or Golgi-derived vesicles. The SCV itself has features of a novel organelle and the fate of this compartment is controlled by the pathogen. Previous observations indicated that the SCV is arrested in the state of late endosomal compartment, but recent studies using advanced ultrastructural analyses and live cell studies indicate a complex and highly dynamic interaction of the intracellular Salmonella and their host cells.
Further reading: Salmonella: From Genome to Function
from Roopa Rajashekar and Michael Hensel writing in Salmonella: From Genome to Function
Salmonella enterica is a facultative intracellular pathogen that resides in a unique membrane-bound compartment, referred to as Salmonella-containing vacuole or SCV. Within the SCV, Salmonella is able to survive the antimicrobial activities of phagocytic cells and can rapidly multiply in a variety of host cells. Intracellular life of Salmonella is dependent on a large number of virulence traits, but the function of the type III secretion system (T3SS) encoded by Salmonella Pathogenicity Island 2 (SPI2) is of central importance. Although more than 20 effector proteins have been identified as translocated by the SPI2-T3SS, the molecular function and contribution to intracellular live is only known for a few of these proteins. Intracellular Salmonella modify basic functions of the host cell such as the structure of the microtubule cytoskeleton and induce a massive reorganization of vesicular transport and the endosomal system. Unique phenomena are the SPI2-dependent induction of extensive tubular membrane aggregations of endosomal or Golgi-derived vesicles. The SCV itself has features of a novel organelle and the fate of this compartment is controlled by the pathogen. Previous observations indicated that the SCV is arrested in the state of late endosomal compartment, but recent studies using advanced ultrastructural analyses and live cell studies indicate a complex and highly dynamic interaction of the intracellular Salmonella and their host cells.
Further reading: Salmonella: From Genome to Function
Salmonella virulence factors
Salmonella secreted virulence factors
from Fred Heffron, George Niemann, Hyunjin Yoon, Afshan Kidwai, Roslyn Brown, Jason McDermott, Richard Smith and Joshua Adkins writing in Salmonella: From Genome to Function
Research in the past twenty years has shown that Salmonella precisely manipulates their host by hierarchical secretion of virulence factors (effectors). More than 40 secreted virulence factors have been identified in Salmonella, but the function and mammalian targets of only a few are known. Effectors are directed to specific sub-cellular compartments and mammalian targets, and they mediate a diverse array of activities. Thus, the first half of this review focuses upon our understanding of effector mechanisms and their roles during infection.
However, the known effector repertoire is incomplete and the second half of this review places an emphasis on discovery. Computer analysis identified common secretion motifs and predicted that as many as 300 additional proteins may be secreted by Salmonella. In fact, mass spectrometry analysis identified a more complete secretome and found many novel, uncharacterized effector proteins. Several effectors identified in this study were small proteins of only 30-100 amino acids in length, suggesting that they are not enzymes but agonists or antagonists of specific host factors. One surprise from the mass spectrometry analysis was the identification of proteins that are secreted to mammalian cells via outer membrane vesicles. Complete characterization of the bewildering array of secreted proteins will take many years.
Further reading: Salmonella: From Genome to Function | Bacterial Secreted Proteins
from Fred Heffron, George Niemann, Hyunjin Yoon, Afshan Kidwai, Roslyn Brown, Jason McDermott, Richard Smith and Joshua Adkins writing in Salmonella: From Genome to Function
Research in the past twenty years has shown that Salmonella precisely manipulates their host by hierarchical secretion of virulence factors (effectors). More than 40 secreted virulence factors have been identified in Salmonella, but the function and mammalian targets of only a few are known. Effectors are directed to specific sub-cellular compartments and mammalian targets, and they mediate a diverse array of activities. Thus, the first half of this review focuses upon our understanding of effector mechanisms and their roles during infection.
However, the known effector repertoire is incomplete and the second half of this review places an emphasis on discovery. Computer analysis identified common secretion motifs and predicted that as many as 300 additional proteins may be secreted by Salmonella. In fact, mass spectrometry analysis identified a more complete secretome and found many novel, uncharacterized effector proteins. Several effectors identified in this study were small proteins of only 30-100 amino acids in length, suggesting that they are not enzymes but agonists or antagonists of specific host factors. One surprise from the mass spectrometry analysis was the identification of proteins that are secreted to mammalian cells via outer membrane vesicles. Complete characterization of the bewildering array of secreted proteins will take many years.
Further reading: Salmonella: From Genome to Function | Bacterial Secreted Proteins
Flagella of Salmonella
New insights into the role and formation of flagella in Salmonella
from Rasika M. Harshey writing in Salmonella: From Genome to Function
The flagellum of Salmonella enterica serovar Typhimurium is the best studied of all flagellar systems. The major function of the flagellum is to enable swimming and chemotaxis in liquid media, and swarming on surfaces. New structural information, along with biochemical, physicochemical and genetic analyses has greatly accelerated our understanding of the self-assembly of this highly sophisticated nano-machine. The study of swarming motility is a relatively new field, but has begun to reveal new roles for the flagellum, new functions for motility genes and new regulatory circuits that control the decision between motility and sessility. Morphological and functional similarities between flagella and needle complexes, discovery of partial flagellar structures that likely function in export rather than motility, and a rapidly accumulating genome database are gradually illuminating the evolutionary origins of the flagellum.
Further reading: Salmonella: From Genome to Function | Pili and Flagella
from Rasika M. Harshey writing in Salmonella: From Genome to Function
The flagellum of Salmonella enterica serovar Typhimurium is the best studied of all flagellar systems. The major function of the flagellum is to enable swimming and chemotaxis in liquid media, and swarming on surfaces. New structural information, along with biochemical, physicochemical and genetic analyses has greatly accelerated our understanding of the self-assembly of this highly sophisticated nano-machine. The study of swarming motility is a relatively new field, but has begun to reveal new roles for the flagellum, new functions for motility genes and new regulatory circuits that control the decision between motility and sessility. Morphological and functional similarities between flagella and needle complexes, discovery of partial flagellar structures that likely function in export rather than motility, and a rapidly accumulating genome database are gradually illuminating the evolutionary origins of the flagellum.
Further reading: Salmonella: From Genome to Function | Pili and Flagella
Fimbriae of Salmonella
Fimbrial signature arrangements in Salmonella
from Sean-Paul Nuccio, Nicholas R. Thomson, Maria C. Fookes and Andreas J. Bäumler writing in Salmonella: From Genome to Function
The complement of fimbrial operons held within a genome represents one of the key differentiating features of the sequenced Salmonella serovars and one of the single largest sources of genetic diversity. Generically described as filamentous non-flagellar surface appendages, fimbriae (also known as pili) typically imbue an adhesive trait to the cells expressing them. While much is known about the general biology of fimbrial assembly mechanisms, the role of these structures in Salmonella pathogenesis remains poorly characterized. Here we present fimbrial operon data gathered from the seventeen completed Salmonella genome sequences and discuss its implications in Salmonella pathogenesis and dissemination.
Further reading: Salmonella: From Genome to Function | Pili and Flagella
from Sean-Paul Nuccio, Nicholas R. Thomson, Maria C. Fookes and Andreas J. Bäumler writing in Salmonella: From Genome to Function
The complement of fimbrial operons held within a genome represents one of the key differentiating features of the sequenced Salmonella serovars and one of the single largest sources of genetic diversity. Generically described as filamentous non-flagellar surface appendages, fimbriae (also known as pili) typically imbue an adhesive trait to the cells expressing them. While much is known about the general biology of fimbrial assembly mechanisms, the role of these structures in Salmonella pathogenesis remains poorly characterized. Here we present fimbrial operon data gathered from the seventeen completed Salmonella genome sequences and discuss its implications in Salmonella pathogenesis and dissemination.
Further reading: Salmonella: From Genome to Function | Pili and Flagella
Small RNAs of Salmonella
The small RNAs of Salmonella
from Sridhar Javayel, Kai Papenfort and Jörg Vogel writing in Salmonella: From Genome to Function
To date, close to one hundred distinct small noncoding RNAs (sRNAs) have been identified in Salmonella by a variety of biocomputational or wet-lab approaches including RNA sequencing. The function of more than twenty of these sRNAs is known from studies in Salmonella itself or can be inferred from conserved homologs in E. coli Many of these sRNAs act in conjunction with the RNA-chaperone Hfq to post-transcriptionally repress or activate trans-encoded target genes, but cis-antisense RNAs and regulators of protein activity are also abundantly present. In addition to a large number of sRNAs conserved in other enteric bacteria, Salmonella also expresses a set of sRNAs specific to this genus. Interestingly, such regulators have been shown to control the expression of conserved genes encoded on the "core" Salmonella genome. Conversely, conserved sRNA can act as regulators of recently acquired Salmonella-specific genes, indicating significant cross-talk of conserved and horizontally acquired elements at the RNA level. A recent review covers strategies for the identification of sRNAs as well as their characterized functional roles in Salmonella.
Further reading: Salmonella: From Genome to Function | RNA and the Regulation of Gene Expression
from Sridhar Javayel, Kai Papenfort and Jörg Vogel writing in Salmonella: From Genome to Function
To date, close to one hundred distinct small noncoding RNAs (sRNAs) have been identified in Salmonella by a variety of biocomputational or wet-lab approaches including RNA sequencing. The function of more than twenty of these sRNAs is known from studies in Salmonella itself or can be inferred from conserved homologs in E. coli Many of these sRNAs act in conjunction with the RNA-chaperone Hfq to post-transcriptionally repress or activate trans-encoded target genes, but cis-antisense RNAs and regulators of protein activity are also abundantly present. In addition to a large number of sRNAs conserved in other enteric bacteria, Salmonella also expresses a set of sRNAs specific to this genus. Interestingly, such regulators have been shown to control the expression of conserved genes encoded on the "core" Salmonella genome. Conversely, conserved sRNA can act as regulators of recently acquired Salmonella-specific genes, indicating significant cross-talk of conserved and horizontally acquired elements at the RNA level. A recent review covers strategies for the identification of sRNAs as well as their characterized functional roles in Salmonella.
Further reading: Salmonella: From Genome to Function | RNA and the Regulation of Gene Expression
Genomics and Pathogenesis of Salmonella
Genomics and Pathogenesis of Salmonella enterica serovars Typhi and Paratyphi A
from Kathryn E Holt, Tim T Perkins, Gordon Dougan and Robert A Kingsley writing in Salmonella: From Genome to Function
The genomics era has transformed the way that we can study bacterial pathogens. The availability of two complete and 17 draft genomes of S. Typhi has made it possible to study the phylogenetic structure of this pathogen in unparalleled resolution, monitor gene flux, accumulation of pseudogenes, neutral mutations and loci under selective pressure. We describe the molecular basis of Salmonella Typhi pathogenesis, in particular where genomics has contributed to our understanding in the past decade. Potentially important S. Typhi-specific virulence determinants include the Vi polysaccharide capsule, the type IV pilus, and a unique repertoire of fimbria. These may account for key differences in the disease outcome of this pathogen compared with non-typhoidal serotypes. Genome comparison with the closely related serotype S. Paratyphi A identifies a core set of pseudogenes, some of which emerged independently, that may define important features of genome degradation associated with host restriction and pathogenesis of invasive disease. Geo-phylogenetics of S. Typhi constructed from single nucleotide polymorphism data from high throughput draft genome sequences is now being applied to study molecular epidemiology in the field.
Further reading: Salmonella: From Genome to Function
from Kathryn E Holt, Tim T Perkins, Gordon Dougan and Robert A Kingsley writing in Salmonella: From Genome to Function
The genomics era has transformed the way that we can study bacterial pathogens. The availability of two complete and 17 draft genomes of S. Typhi has made it possible to study the phylogenetic structure of this pathogen in unparalleled resolution, monitor gene flux, accumulation of pseudogenes, neutral mutations and loci under selective pressure. We describe the molecular basis of Salmonella Typhi pathogenesis, in particular where genomics has contributed to our understanding in the past decade. Potentially important S. Typhi-specific virulence determinants include the Vi polysaccharide capsule, the type IV pilus, and a unique repertoire of fimbria. These may account for key differences in the disease outcome of this pathogen compared with non-typhoidal serotypes. Genome comparison with the closely related serotype S. Paratyphi A identifies a core set of pseudogenes, some of which emerged independently, that may define important features of genome degradation associated with host restriction and pathogenesis of invasive disease. Geo-phylogenetics of S. Typhi constructed from single nucleotide polymorphism data from high throughput draft genome sequences is now being applied to study molecular epidemiology in the field.
Further reading: Salmonella: From Genome to Function
Salmonella evolution
Evolutionary trends associated with niche specialization as modeled by whole genome analysis of egg-contaminating Salmonella enterica serovar Enteritidis
from Jean Guard, Devendra Shah, Cesar A. Morales and Doug Call writing in Salmonella: From Genome to Function
The mosaic nature of the Salmonella enterica genome facilitates its access to multiple environments. Many large scale genomic events have been described that contribute to the combinatorial complexity of the pathogenic Salmonellae. However, the impact of small scale genetic change occurring at the level of single nucleotide polymorphism (SNP) on the emergence of niche specialization is just now becoming appreciated. A recent review describes concepts behind the evolution that culminated in the remarkable ability of Salmonella enterica serovar Enteritidis to contaminate and survive in the internal content of eggs produced by otherwise healthy hens. Evidence suggests that combinations of SNPs facilitate niche specialization by Salmonella enterica. However, few typing methods incorporate unbiased strategies for their detection. Selection of appropriate biological assays for ranking SNPs and combinations of SNPs for their impact on the ability of Salmonella enterica to propagate outbreaks, pandemics and disease will be a significant challenge to improve the safety of the food supply.
Further reading: Salmonella: From Genome to Function
from Jean Guard, Devendra Shah, Cesar A. Morales and Doug Call writing in Salmonella: From Genome to Function
The mosaic nature of the Salmonella enterica genome facilitates its access to multiple environments. Many large scale genomic events have been described that contribute to the combinatorial complexity of the pathogenic Salmonellae. However, the impact of small scale genetic change occurring at the level of single nucleotide polymorphism (SNP) on the emergence of niche specialization is just now becoming appreciated. A recent review describes concepts behind the evolution that culminated in the remarkable ability of Salmonella enterica serovar Enteritidis to contaminate and survive in the internal content of eggs produced by otherwise healthy hens. Evidence suggests that combinations of SNPs facilitate niche specialization by Salmonella enterica. However, few typing methods incorporate unbiased strategies for their detection. Selection of appropriate biological assays for ranking SNPs and combinations of SNPs for their impact on the ability of Salmonella enterica to propagate outbreaks, pandemics and disease will be a significant challenge to improve the safety of the food supply.
Further reading: Salmonella: From Genome to Function
Salmonella survival
High-throughput screening to determine the genetic requirements for Salmonella survival under different growth conditions
from Mollie Megan Reynolds, Rocio Canals, Michael McClelland and Helene Andrews-Polymenis writing in Salmonella: From Genome to Function
Salmonella species are capable of survival in a wide range of niches, both in the environment and in an infected host. Genetic requirements for survival of Salmonella in different niches have traditionally been identified using gene expression and forward genetics. The availability of complete genome sequences, microarray technology, and cost-effective new sequencing capabilities enabled increasingly efficient high-throughput analyses of Salmonella genomes to identify elements that contribute to survival in these niches. A recent review describes many of the high-throughput tools that have been developed over the past two decades, and the genetic requirements for Salmonella survival that have been identified using these techniques.
Further reading: Salmonella: From Genome to Function
from Mollie Megan Reynolds, Rocio Canals, Michael McClelland and Helene Andrews-Polymenis writing in Salmonella: From Genome to Function
Salmonella species are capable of survival in a wide range of niches, both in the environment and in an infected host. Genetic requirements for survival of Salmonella in different niches have traditionally been identified using gene expression and forward genetics. The availability of complete genome sequences, microarray technology, and cost-effective new sequencing capabilities enabled increasingly efficient high-throughput analyses of Salmonella genomes to identify elements that contribute to survival in these niches. A recent review describes many of the high-throughput tools that have been developed over the past two decades, and the genetic requirements for Salmonella survival that have been identified using these techniques.
Further reading: Salmonella: From Genome to Function
Salmonella genomes
Comparison of Salmonella genomes
from Ye Feng, Wei-Qiao Liu, Kenneth E. Sanderson, and Shu-Lin Liu writing in Salmonella: From Genome to Function:
Salmonella contains over 2600 known lineages, each with distinct biological characteristics, including differences in the niche in which they dwell and the nature of diseases they may cause in their hosts. Genomic sequence analysis is beginning to reveal the genetic basis that determines the phenotypic differences among them. Comparison of eight sequenced genomes of Salmonella subgroup I lineages, which infect warm-blooded animals including humans, demonstrates that these pathogens share about 90% of their genes (the "core" genome), with the remaining ca. 10% genes being unique to each of the lineages (the "accessory" genome). Prophages and Salmonella Pathogenicity Islands (SPIs) are the main components of the accessory genome. Insertion of large DNA segments, such as SPI7 in S. Typhi, may disrupt physical balance of the genome between replication origin and terminus and rearrangements of the genome, such as inversions or translocations mediated by homologous sites (rrn operons, prophages, IS200, etc.) may accelerate rebalancing of the genome. Laterally transferred genes are the main driving force in Salmonella evolution and speciation; evidence exists indicating that mismatch repair genes may spontaneously regulate bacterial mutability through allele conversion to facilitate or inhibit incorporation of foreign DNA. Further studies may help elucidate the genetic basis of distinct pathogeneses and host ranges among the Salmonella pathogens.
Further reading: Salmonella: From Genome to Function
from Ye Feng, Wei-Qiao Liu, Kenneth E. Sanderson, and Shu-Lin Liu writing in Salmonella: From Genome to Function:
Salmonella contains over 2600 known lineages, each with distinct biological characteristics, including differences in the niche in which they dwell and the nature of diseases they may cause in their hosts. Genomic sequence analysis is beginning to reveal the genetic basis that determines the phenotypic differences among them. Comparison of eight sequenced genomes of Salmonella subgroup I lineages, which infect warm-blooded animals including humans, demonstrates that these pathogens share about 90% of their genes (the "core" genome), with the remaining ca. 10% genes being unique to each of the lineages (the "accessory" genome). Prophages and Salmonella Pathogenicity Islands (SPIs) are the main components of the accessory genome. Insertion of large DNA segments, such as SPI7 in S. Typhi, may disrupt physical balance of the genome between replication origin and terminus and rearrangements of the genome, such as inversions or translocations mediated by homologous sites (rrn operons, prophages, IS200, etc.) may accelerate rebalancing of the genome. Laterally transferred genes are the main driving force in Salmonella evolution and speciation; evidence exists indicating that mismatch repair genes may spontaneously regulate bacterial mutability through allele conversion to facilitate or inhibit incorporation of foreign DNA. Further studies may help elucidate the genetic basis of distinct pathogeneses and host ranges among the Salmonella pathogens.
Further reading: Salmonella: From Genome to Function
Phages of Salmonella
Typing phages and prophages of Salmonella
from Wolfgang Rabsch, Sandra Truepschuch, Daniel Windhorst and Roman G. Gerlach writing in Salmonella: From Genome to Function:
Most Salmonella strains contain prophages or remnant phages and release them spontaneously. Special bacteriophages were developed and used in phage typing systems for epidemiological work all over the world since 1947 to control salmonellosis. This method provides fast and inexpensive characterization of frequent serovars such as S. Typhimurium or S. Typhi on the sub-serovar level and is especially useful for primary analysis before investigation by other, more expensive molecular techniques such as sequencing. Prophages are themselves not only variable elements in a chromosome but also variable by module exchange within the prophage genome, thus providing a high discriminating power. The availability of several genome sequences of different Salmonella serovars has recently led to the identification of new prophage-like elements. The prophages present in serovars Typhimurium, Enteritidis and Typhi are discussed. Salmonella phages frequently carry foreign DNA, so called morons. These morons are not necessary for phage functions but provide a benefit for the host. A list of some new morons found in different Salmonella serovars is presented. Recently, a monophasic variant of S. Typhimurium mainly belonging to Anderson phage type DT193 has become one of the dominant causes of salmonellosis in Germany and other European countries. These strains with the antigenic formula 4,[5],12:i:- do not express the 2nd phase flagellum. Investigation of their prophage attachment sites showed that the sites for Gifsy-1, Gifsy-2 and ST64B were occupied by the respective prophages. In about 90% of the monophasic DT193 strains the P22/ST64T attachment site was occupied by a novel 18.4 kb fragment, containing several open reading frames with significant similiarity to phage-related genes.
Further reading: Salmonella: From Genome to Function | Bacteriophage: Genetics and Molecular Biology
from Wolfgang Rabsch, Sandra Truepschuch, Daniel Windhorst and Roman G. Gerlach writing in Salmonella: From Genome to Function:
Most Salmonella strains contain prophages or remnant phages and release them spontaneously. Special bacteriophages were developed and used in phage typing systems for epidemiological work all over the world since 1947 to control salmonellosis. This method provides fast and inexpensive characterization of frequent serovars such as S. Typhimurium or S. Typhi on the sub-serovar level and is especially useful for primary analysis before investigation by other, more expensive molecular techniques such as sequencing. Prophages are themselves not only variable elements in a chromosome but also variable by module exchange within the prophage genome, thus providing a high discriminating power. The availability of several genome sequences of different Salmonella serovars has recently led to the identification of new prophage-like elements. The prophages present in serovars Typhimurium, Enteritidis and Typhi are discussed. Salmonella phages frequently carry foreign DNA, so called morons. These morons are not necessary for phage functions but provide a benefit for the host. A list of some new morons found in different Salmonella serovars is presented. Recently, a monophasic variant of S. Typhimurium mainly belonging to Anderson phage type DT193 has become one of the dominant causes of salmonellosis in Germany and other European countries. These strains with the antigenic formula 4,[5],12:i:- do not express the 2nd phase flagellum. Investigation of their prophage attachment sites showed that the sites for Gifsy-1, Gifsy-2 and ST64B were occupied by the respective prophages. In about 90% of the monophasic DT193 strains the P22/ST64T attachment site was occupied by a novel 18.4 kb fragment, containing several open reading frames with significant similiarity to phage-related genes.
Further reading: Salmonella: From Genome to Function | Bacteriophage: Genetics and Molecular Biology
Salmonella classification
New approaches in sub-species level Salmonella classification
from Burkhard Malorny, Elisabeth Hauser and Ralf Dieckmann writing in Salmonella: From Genome to Function:
Salmonellae form a complex group of bacteria consisting of two species, 6 subspecies and more than 2,500 serovars (serotypes). Salmonella identification below species level is most often limited to phenotypic typing methods such as biochemical and serological identification, which are costly, time-consuming and do not always reflect the evolution of Salmonella groups. Newer methods for Salmonella typing and subtyping include genome-based methods such as pulsed field gel electrophoresis (PFGE), Multiple Loci VNTR Analysis (MLVA), Multilocus sequence typing (MLST) and (multiplex-) PCR-based methods. In the last years further molecular typing technologies were evaluated for this purpose. A recent review discusses some of these emerging technologies and gives an outlook on future developments with a focus on oligonucleotide microarrays, spectroscopic methods such as MALDI-TOF mass spectrometry and special developments such as bead-based suspension arrays using Luminex technology and DNA sequence-based approaches. These new techniques promise significant advantages compared to traditional culture-based methods with respect to speed, ease of use, reliability and automation.
Further reading: Salmonella: From Genome to Function
from Burkhard Malorny, Elisabeth Hauser and Ralf Dieckmann writing in Salmonella: From Genome to Function:
Salmonellae form a complex group of bacteria consisting of two species, 6 subspecies and more than 2,500 serovars (serotypes). Salmonella identification below species level is most often limited to phenotypic typing methods such as biochemical and serological identification, which are costly, time-consuming and do not always reflect the evolution of Salmonella groups. Newer methods for Salmonella typing and subtyping include genome-based methods such as pulsed field gel electrophoresis (PFGE), Multiple Loci VNTR Analysis (MLVA), Multilocus sequence typing (MLST) and (multiplex-) PCR-based methods. In the last years further molecular typing technologies were evaluated for this purpose. A recent review discusses some of these emerging technologies and gives an outlook on future developments with a focus on oligonucleotide microarrays, spectroscopic methods such as MALDI-TOF mass spectrometry and special developments such as bead-based suspension arrays using Luminex technology and DNA sequence-based approaches. These new techniques promise significant advantages compared to traditional culture-based methods with respect to speed, ease of use, reliability and automation.
Further reading: Salmonella: From Genome to Function
Neisseria Book Review
I am pleased to provide the following excerpt from a book review of Neisseria: Molecular Mechanisms of Pathogenesis:
"focuses effectively on (the) molecular approach to neisserial pathogenicity ... authoritative reviews of gene regulation, anaerobic survival, genome plasticity, epidemiology, vaccine development and the development of antibiotic resistance ... well-referenced" from Jeff Cole (University of Birmingham, UK) writing in Microbiology Today read more ...
"focuses effectively on (the) molecular approach to neisserial pathogenicity ... authoritative reviews of gene regulation, anaerobic survival, genome plasticity, epidemiology, vaccine development and the development of antibiotic resistance ... well-referenced" from Jeff Cole (University of Birmingham, UK) writing in Microbiology Today read more ...
| Edited by: Caroline Genco and Lee Wetzler "authoritative reviews" (Microbiology Today)ISBN: 978-1-904455-51-6 Publisher: Caister Academic Press Publication Date: January 2010 Cover: hardback |
Streptomyces book
Paul Dyson (Institute of Life Sciences, School of Medicine, Swansea, UK) presents a new book on Streptomyces: Molecular Biology and Biotechnology
Streptomycetes are Gram-positive, high GC-content, sporulating bacteria found predominantly in soil. Streptomycetes are characterised by a complex secondary metabolism producing antibiotic compounds and other metabolites with medicinal properties. In recent years genomic studies, genomic mining and biotechnological approaches have been employed in the search for new antibiotics and other drugs.
With contributions from some of the leading scientists in the field, this volume documents recent research and development in streptomycetes genomics, physiology and metabolism. With a focus on biotechnology and genomics, the book provides an excellent source of up-to-date information. Topics include: genome architecture, conjugative genetic elements, differentiation, protein secretion, central carbon metabolic pathways, regulation of nitrogen assimilation, phosphate control of metabolism, gamma-butyrolactones and their role in antibiotic regulation, clavulanic acid and clavams, genome-guided exploration, gene clusters for bioactive natural products, genomics of cytochromes p450.
Streptomycetes are Gram-positive, high GC-content, sporulating bacteria found predominantly in soil. Streptomycetes are characterised by a complex secondary metabolism producing antibiotic compounds and other metabolites with medicinal properties. In recent years genomic studies, genomic mining and biotechnological approaches have been employed in the search for new antibiotics and other drugs.
With contributions from some of the leading scientists in the field, this volume documents recent research and development in streptomycetes genomics, physiology and metabolism. With a focus on biotechnology and genomics, the book provides an excellent source of up-to-date information. Topics include: genome architecture, conjugative genetic elements, differentiation, protein secretion, central carbon metabolic pathways, regulation of nitrogen assimilation, phosphate control of metabolism, gamma-butyrolactones and their role in antibiotic regulation, clavulanic acid and clavams, genome-guided exploration, gene clusters for bioactive natural products, genomics of cytochromes p450.
 | Edited by: Paul Dyson ISBN: 978-1-904455-77-6 Publisher: Caister Academic Press Publication Date: January 2011 Cover: hardback |
Essential reading for research scientists, biotechnologists, graduate students and other professionals involved in streptomycetes research, antibiotic and antimicrobial development, drug discovery, soil microbiology and related fields. A recommended text for all microbiology laboratories.
Bacterial Histone-Like HU Proteins
Bacterial histone-like HU proteins are critical to maintenance of the nucleoid structure. In addition, they participate in all DNA-dependent functions, including replication, repair, recombination and gene regulation. Their function is typically architectural, inducing a specific DNA topology that promotes assembly of higher-order nucleo-protein structures.
Although HU proteins are highly conserved, individual homologs have been shown to exhibit a wide range of different DNA binding specificities and affinities. The existence of such distinct specificities indicates functional evolution and predicts distinct in vivo roles. Emerging evidence suggests that HU proteins discriminate between DNA target sites based on intrinsic flexure, and that two primary features of protein binding contribute to target site selection: The extent to which protein-mediated DNA kinks are stabilized and a network of surface salt-bridges that modulate interaction between DNA flanking the kinks and the body of the protein.
These features confer target site selection for a specific HU homolog, they suggest the ability of HU to induce different DNA structural deformations depending on substrate, and they explain the distinct binding properties characteristic of HU homologs. Further divergence is evidenced by the existence of HU homologs with an additional lysine-rich domain also found in eukaryotic histone H1.
Further reading: Functional Evolution of Bacterial Histone-Like HU Proteins
Although HU proteins are highly conserved, individual homologs have been shown to exhibit a wide range of different DNA binding specificities and affinities. The existence of such distinct specificities indicates functional evolution and predicts distinct in vivo roles. Emerging evidence suggests that HU proteins discriminate between DNA target sites based on intrinsic flexure, and that two primary features of protein binding contribute to target site selection: The extent to which protein-mediated DNA kinks are stabilized and a network of surface salt-bridges that modulate interaction between DNA flanking the kinks and the body of the protein.
These features confer target site selection for a specific HU homolog, they suggest the ability of HU to induce different DNA structural deformations depending on substrate, and they explain the distinct binding properties characteristic of HU homologs. Further divergence is evidenced by the existence of HU homologs with an additional lysine-rich domain also found in eukaryotic histone H1.
Further reading: Functional Evolution of Bacterial Histone-Like HU Proteins
Bacterial Spores
Endospore-forming bacteria produce some of the most potent toxins known and are important pathogens in hospital-borne infections (Clostridium difficile) food contamination (Bacillus cereus, Clostridium botulinum), wound infestation (Clostridium perfringens, Clostridium tetani) and bioterrorism (Bacillus anthracis).
Bacilli and Clostridia spores form in response to unfavorable environmental conditions and can withstand extremes of heat, radiation, and chemical agents. The spore's durability is even more remarkable considering that dormant spores revert back to actively growing cells almost immediately after nutrients return to the environment. The intrinsic resistance and the ability to remain dormant for long periods make spores the perfect delivery vehicle for infectious diseases.
Further reading: The Ger Receptor Family from Sporulating Bacteria
Bacilli and Clostridia spores form in response to unfavorable environmental conditions and can withstand extremes of heat, radiation, and chemical agents. The spore's durability is even more remarkable considering that dormant spores revert back to actively growing cells almost immediately after nutrients return to the environment. The intrinsic resistance and the ability to remain dormant for long periods make spores the perfect delivery vehicle for infectious diseases.
Further reading: The Ger Receptor Family from Sporulating Bacteria
The Ger Receptor Family
Ger receptor activation is the first committed step in the germination process. Ger receptors are encoded, in general, as tricistronic operons containing three protein-coding genes, the A-, B-, and C-subunits. However, some Ger receptor subunits are encoded as orphan monocistronic genes and yet other ger receptor operons encode duplicated subunit genes.
The A-subunit protein of Ger receptors consist of five or six predicted membrane-spanning domains, as well as large N- and C-terminal hydrophilic domains. A-subunit proteins share significant homology to SpoVAF, a late-sporulation protein with no known function. Intriguingly, Ger receptors have been shown to interact with proteins from the spoVA operon. Whether these interactions are relevant to spore germination remains to be elucidated.
Further reading: The Ger Receptor Family from Sporulating Bacteria
The A-subunit protein of Ger receptors consist of five or six predicted membrane-spanning domains, as well as large N- and C-terminal hydrophilic domains. A-subunit proteins share significant homology to SpoVAF, a late-sporulation protein with no known function. Intriguingly, Ger receptors have been shown to interact with proteins from the spoVA operon. Whether these interactions are relevant to spore germination remains to be elucidated.
Further reading: The Ger Receptor Family from Sporulating Bacteria
Neisseria Book Review
I am pleased to provide the following excerpt from a book review of Neisseria: Molecular Mechanisms of Pathogenesis:
"written by outstanding and internationally highly recognized experts in the Neisseria research field ... The chapters are of the highest scientific quality including links to central primary publications on the different topics ... an excellent monography for the specialist" from Arzneimittelforschung/Drug Research (2010) 60: 226-227 read more ...
"written by outstanding and internationally highly recognized experts in the Neisseria research field ... The chapters are of the highest scientific quality including links to central primary publications on the different topics ... an excellent monography for the specialist" from Arzneimittelforschung/Drug Research (2010) 60: 226-227 read more ...
| Edited by: Caroline Genco and Lee Wetzler "a comprehensive update" (Society for Microbial Ecology and Disease)ISBN: 978-1-904455-51-6 Publisher: Caister Academic Press Publication Date: January 2010 Cover: Hardback |
Sensory Mechanisms in Bacteria
from Sensory Mechanisms in Bacteria: Molecular Aspects of Signal Recognition
Bacteria have evolved extraordinary abilities to detect physical and chemical signals, both within their own cells and in the extracellular environment. The interaction of a signal with its receptor (usually a protein or RNA molecule) triggers a series of events that lead to reprogramming of cellular physiology, typically as a consequence of altered patterns of gene expression. In this way, the bacterial cell is able to mount appropriate and effective responses to changing physical and/or chemical environments. The versatility with which many bacteria adapt to environmental change underlies many important aspects of microbiology. For example, pathogens encounter multiple environments as they invade a host from the outside, and then progress through different sites within host tissues. There is growing evidence that pathogenic bacteria make use of physical and chemical cues to signal their presence in a suitable host, and need to adapt to the host environment in order to mount a successful infection. On the other hand, it should not be assumed that all signals to which bacteria must respond originate in the extracellular environment. For many species, even the cosseted life in a laboratory shake flask is 'stressful', in the sense that there is often a need to avoid or reverse the effects of harmful intermediates or by-products of metabolism. For example, all organisms that use dioxygen as a terminal electron acceptor have to deal with the reactive oxygen species that arise as adventitious by-products of aerobic metabolism. In bacteria, multiple protein receptors for oxygen radicals have been described, which control the expression of genes encoding enzymes that detoxify oxygen radicals or repair the damage that they cause.
Further reading: Sensory Mechanisms in Bacteria: Molecular Aspects of Signal Recognition
Bacteria have evolved extraordinary abilities to detect physical and chemical signals, both within their own cells and in the extracellular environment. The interaction of a signal with its receptor (usually a protein or RNA molecule) triggers a series of events that lead to reprogramming of cellular physiology, typically as a consequence of altered patterns of gene expression. In this way, the bacterial cell is able to mount appropriate and effective responses to changing physical and/or chemical environments. The versatility with which many bacteria adapt to environmental change underlies many important aspects of microbiology. For example, pathogens encounter multiple environments as they invade a host from the outside, and then progress through different sites within host tissues. There is growing evidence that pathogenic bacteria make use of physical and chemical cues to signal their presence in a suitable host, and need to adapt to the host environment in order to mount a successful infection. On the other hand, it should not be assumed that all signals to which bacteria must respond originate in the extracellular environment. For many species, even the cosseted life in a laboratory shake flask is 'stressful', in the sense that there is often a need to avoid or reverse the effects of harmful intermediates or by-products of metabolism. For example, all organisms that use dioxygen as a terminal electron acceptor have to deal with the reactive oxygen species that arise as adventitious by-products of aerobic metabolism. In bacteria, multiple protein receptors for oxygen radicals have been described, which control the expression of genes encoding enzymes that detoxify oxygen radicals or repair the damage that they cause.
Further reading: Sensory Mechanisms in Bacteria: Molecular Aspects of Signal Recognition
Signal Recognition Book
Stephen Spiro and Ray Dixon (Texas, USA and Norwich,UK; respectively) present a new publication Sensory Mechanisms in Bacteria: Molecular Aspects of Signal Recognition
This book reviews a selection of important model systems, providing a timely snapshot of the current state of research in the field. The book opens with an introductory chapter that reviews the diversity of signal recognition mechanisms, illustrating the breadth of the field. Subsequent chapters include descriptions of the sensing of ligands (alpha-ketoglutarate, adenylate energy charge, glutamine and xenobiotic compounds), chemoreceptors, iron-sulfur cluster-based sensors, metal-dependent and metal-responsive sensors, thiol-based sensors, and PDZ domains as sensors of other proteins read more ....
This book reviews a selection of important model systems, providing a timely snapshot of the current state of research in the field. The book opens with an introductory chapter that reviews the diversity of signal recognition mechanisms, illustrating the breadth of the field. Subsequent chapters include descriptions of the sensing of ligands (alpha-ketoglutarate, adenylate energy charge, glutamine and xenobiotic compounds), chemoreceptors, iron-sulfur cluster-based sensors, metal-dependent and metal-responsive sensors, thiol-based sensors, and PDZ domains as sensors of other proteins read more ....
 | Edited by: Stephen Spiro and Ray Dixon ISBN: 978-1-904455-69-1 Publisher: Caister Academic Press Publication Date: September 2010 Cover: Hardback |
Probiotic properties of bifidobacteria
from Maddalena Rossi and Alberto Amaretti in Bifidobacteria: Genomics and Molecular Aspects
Bifidobacteria are major components of the indigenous bacterial population present in the human gut and are arguably most relevant to the health-promoting properties that have been attributed to elements of this microbiota. They exert a range of beneficial health effects, including the regulation of intestinal microbial homeostasis, the inhibition of pathogens and harmful bacteria that colonize and/or infect the gut mucosa, the modulation of local and systemic immune responses, the repression of procarcinogenic enzymatic activities within the microbiota, the production of vitamins, and the bioconversion of a number of dietary compounds into bioactive molecules. Health-promoting properties of members of the genus Bifidobacterium have been reported but research is still necessary for an in depth understanding of the probiotic function. In fact, although experimental evidence of the probiotic effectiveness of bifidobacteria has a long history, little information is available on the molecular mechanisms underlying the health-promoting claims, especially on such complex phenomena as anticarcinogenic and anti-inflammatory effects.
Further reading:
Bifidobacteria are major components of the indigenous bacterial population present in the human gut and are arguably most relevant to the health-promoting properties that have been attributed to elements of this microbiota. They exert a range of beneficial health effects, including the regulation of intestinal microbial homeostasis, the inhibition of pathogens and harmful bacteria that colonize and/or infect the gut mucosa, the modulation of local and systemic immune responses, the repression of procarcinogenic enzymatic activities within the microbiota, the production of vitamins, and the bioconversion of a number of dietary compounds into bioactive molecules. Health-promoting properties of members of the genus Bifidobacterium have been reported but research is still necessary for an in depth understanding of the probiotic function. In fact, although experimental evidence of the probiotic effectiveness of bifidobacteria has a long history, little information is available on the molecular mechanisms underlying the health-promoting claims, especially on such complex phenomena as anticarcinogenic and anti-inflammatory effects.
Further reading:
Metabolism of bifidobacteria
from David A. Sela, Neil P. J Price and David A. Mills in Bifidobacteria: Genomics and Molecular Aspects
The genus Bifidobacterium possesses a unique fructose-6-phosphate phosphoketolase pathway employed to ferment carbohydrates. Much metabolic research on bifidobacteria has focused on oligosaccharide metabolism as these carbohydrate polymers are available in their otherwise nutrient-limited habitats. Interestingly, infant-associated bifidobacterial phylotypes appear to have evolved the ability to ferment milk oligosaccharides, whereas adult-associated species utilize plant oligosaccharides, consistent with what they encounter in their respective environments. As breast-fed infants often harbor bifidobacteria dominated gut consortia, there have been numerous applications to mimic the bifidogenic properties of milk oligosaccharides. These are broadly classified as plant-derived fructo-oligosaccharides or dairy-derived galacto-oligosaccharides, which are differentially metabolized and distinct from milk oligosaccharide catabolism.
Further reading:
The genus Bifidobacterium possesses a unique fructose-6-phosphate phosphoketolase pathway employed to ferment carbohydrates. Much metabolic research on bifidobacteria has focused on oligosaccharide metabolism as these carbohydrate polymers are available in their otherwise nutrient-limited habitats. Interestingly, infant-associated bifidobacterial phylotypes appear to have evolved the ability to ferment milk oligosaccharides, whereas adult-associated species utilize plant oligosaccharides, consistent with what they encounter in their respective environments. As breast-fed infants often harbor bifidobacteria dominated gut consortia, there have been numerous applications to mimic the bifidogenic properties of milk oligosaccharides. These are broadly classified as plant-derived fructo-oligosaccharides or dairy-derived galacto-oligosaccharides, which are differentially metabolized and distinct from milk oligosaccharide catabolism.
Further reading:
Genomics of Bifidobacteria
from Marco Ventura, Francesca Turroni, Francesca Bottacini and Douwe van Sinderen in Bifidobacteria: Genomics and Molecular Aspects
During recent years microbiological research has been fundamentally changed by the ever increasing number of publicly available bacterial whole-genome sequences. This sequence information has largely affected our understanding of the metabolic capabilities, genetics and phylogeny of bacteria. Bifidobacteria constitute one of the key microbial groups of the human intestinal microbiota, due to their perceived positive contribution to maintain a balanced gut homeostasis. In recent years bifidobacteria have drawn much scientific attention because of their use as live bacteria in numerous food preparations with several health-related claims. For this reason these bifidobacteria represent a developing area of scientific interest with respect to genomics, molecular biology, genetics and physiology. Recent genome sequencing of different bifidobacterial species has provided the complete genetic make-up of these bacteria.
Further reading:
During recent years microbiological research has been fundamentally changed by the ever increasing number of publicly available bacterial whole-genome sequences. This sequence information has largely affected our understanding of the metabolic capabilities, genetics and phylogeny of bacteria. Bifidobacteria constitute one of the key microbial groups of the human intestinal microbiota, due to their perceived positive contribution to maintain a balanced gut homeostasis. In recent years bifidobacteria have drawn much scientific attention because of their use as live bacteria in numerous food preparations with several health-related claims. For this reason these bifidobacteria represent a developing area of scientific interest with respect to genomics, molecular biology, genetics and physiology. Recent genome sequencing of different bifidobacterial species has provided the complete genetic make-up of these bacteria.
Further reading:
Bifidobacteria
from Bifidobacteria: Genomics and Molecular Aspects
Bifidobacteria are Gram-positive anaerobic bacteria, found naturally in the gut of humans and other mammals. They are widely used as probiotic organisms in a vast array of formulations for the prevention, alleviation and treatment of many intestinal disorders. However bifidobacteria are fastidious microorganisms and difficult to study in the laboratory, so until recently, understanding of their genetics lagged behind that of other high GC content Gram-positive bacteria. The application of modern whole genome approaches to bifidobacteria research has changed all of this, permitting the accumulation of an impressive amount of data, something that could not have been foreseen a few years ago.
Among the myriad of bacterial species that inhabit the human gut and the gut of many animals, bifidobacteria are almost certainly the microbial group that has the greatest effect on the health of the host. In most people, bifidobacteria are present in high numbers (108-109 cells/g of intestinal content) throughout their lives, although each individual permanently harbours only several species or specific biotypes. Apart from lactobacilli, bifidobacteria is the only intestinal microbial group that is generally recognized to possess such positive characteristics through its capacity to produce short chain fatty acids, vitamins, bacteriocins and antibiotic-like substances, and of exerting immunomodulating and immunostimulating activities. Moreover, the bifidobacterial species so far identified lack enzyme urease, azo- and nitro-reductase, beta-glucuronidase and alpha-dehydrolase that exert enzymatic and metabolic effects that are perceived to be toxic to the host. Consequently, bifidobacteria can be considered as valuable probiotics and today they are not only used in the food industry to relieve and treat many intestinal disorders, but they are increasingly attracting the scientific interest of clinicians and researchers.
Further reading:
Bifidobacteria are Gram-positive anaerobic bacteria, found naturally in the gut of humans and other mammals. They are widely used as probiotic organisms in a vast array of formulations for the prevention, alleviation and treatment of many intestinal disorders. However bifidobacteria are fastidious microorganisms and difficult to study in the laboratory, so until recently, understanding of their genetics lagged behind that of other high GC content Gram-positive bacteria. The application of modern whole genome approaches to bifidobacteria research has changed all of this, permitting the accumulation of an impressive amount of data, something that could not have been foreseen a few years ago.
Among the myriad of bacterial species that inhabit the human gut and the gut of many animals, bifidobacteria are almost certainly the microbial group that has the greatest effect on the health of the host. In most people, bifidobacteria are present in high numbers (108-109 cells/g of intestinal content) throughout their lives, although each individual permanently harbours only several species or specific biotypes. Apart from lactobacilli, bifidobacteria is the only intestinal microbial group that is generally recognized to possess such positive characteristics through its capacity to produce short chain fatty acids, vitamins, bacteriocins and antibiotic-like substances, and of exerting immunomodulating and immunostimulating activities. Moreover, the bifidobacterial species so far identified lack enzyme urease, azo- and nitro-reductase, beta-glucuronidase and alpha-dehydrolase that exert enzymatic and metabolic effects that are perceived to be toxic to the host. Consequently, bifidobacteria can be considered as valuable probiotics and today they are not only used in the food industry to relieve and treat many intestinal disorders, but they are increasingly attracting the scientific interest of clinicians and researchers.
Further reading:
Bifidobacteria book
Baltasar Mayo and Douwe van Sinderen (Asturias, Spain and Cork, Ireland; respectively) present a new publication Bifidobacteria: Genomics and Molecular Aspects
This book brings together the expertise and enthusiasm of leading bifidobacteria experts from around the world to provide a state-of-the art overview of the molecular biology and genomics of this important microbial genus. Topics include: ecology, genomics, comparative genomics, metabolism, acid and bile resistance, stress response, probiotic properties, antimicrobial activity, interaction with the intestinal mucosa, safety assessment of bifidobacteria, synthesis and utilization of exopolysaccharides and prebiotics, antibiotic resistance/susceptibility profiles, viability and stability in commercial preparations, mobile genetic elements, cloning vectors and genetic manipulation of bifidobacteria read more ...
This book brings together the expertise and enthusiasm of leading bifidobacteria experts from around the world to provide a state-of-the art overview of the molecular biology and genomics of this important microbial genus. Topics include: ecology, genomics, comparative genomics, metabolism, acid and bile resistance, stress response, probiotic properties, antimicrobial activity, interaction with the intestinal mucosa, safety assessment of bifidobacteria, synthesis and utilization of exopolysaccharides and prebiotics, antibiotic resistance/susceptibility profiles, viability and stability in commercial preparations, mobile genetic elements, cloning vectors and genetic manipulation of bifidobacteria read more ...
| Edited by: Baltasar Mayo and Douwe van Sinderen ISBN: 978-1-904455-68-4 Publisher: Caister Academic Press Publication Date: August 2010 Cover: Hardback |
Salmonella book
A new book entitled Salmonella: From Genome to Function has just been announced:
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 | Edited by: Steffen Porwollik ISBN: 978-1-904455-73-8 Publisher: Caister Academic Press Publication Date: January 2011 Cover: Hardback read more ... |
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H pylori book review
Excerpt from a recent book review of Helicobacter pylori: Molecular Genetics and Cellular Biology.
"contains 12 chapters that update key areas of basic research ... this book should be useful for researchers in the H. pylori field as well as anyone working in closely related organisms." from D. Scott Merrell (Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA) writing in The Quarterly Review of Biology (2010) 85: 110. read more ...
"contains 12 chapters that update key areas of basic research ... this book should be useful for researchers in the H. pylori field as well as anyone working in closely related organisms." from D. Scott Merrell (Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA) writing in The Quarterly Review of Biology (2010) 85: 110. read more ...