Begomovirus
Emergence of Begomovirus Diseases
from Enrique Moriones, Jesus Navas-Castillo and Juan-Antonio Díaz-Pendón writing in Recent Advances in Plant Virology
Begomoviruses (genus Begomovirus, family Geminiviridae) rank among the top of the most important plant viruses causing disease of severe consequences in economically and socially relevant crops. From the early 1990s, a rapid emergence and geographic expansion of begomoviruses has occurred worldwide. As a result, these viruses have become the most destructive group of plant viruses in tropical and subtropical regions of the world. Their emergence is associated with the emergence of populations of the insect vector, the whitefly Bemisia tabaci, probably due to increased plant trading between distantly separated geographical regions and changes in agricultural practices. Human activity seems to have been a major factor promoting emergence of begomoviruses. Other factors also drive emergence.
Further reading: Recent Advances in Plant Virology | Virology Publications
from Enrique Moriones, Jesus Navas-Castillo and Juan-Antonio Díaz-Pendón writing in Recent Advances in Plant Virology
Begomoviruses (genus Begomovirus, family Geminiviridae) rank among the top of the most important plant viruses causing disease of severe consequences in economically and socially relevant crops. From the early 1990s, a rapid emergence and geographic expansion of begomoviruses has occurred worldwide. As a result, these viruses have become the most destructive group of plant viruses in tropical and subtropical regions of the world. Their emergence is associated with the emergence of populations of the insect vector, the whitefly Bemisia tabaci, probably due to increased plant trading between distantly separated geographical regions and changes in agricultural practices. Human activity seems to have been a major factor promoting emergence of begomoviruses. Other factors also drive emergence.
Further reading: Recent Advances in Plant Virology | Virology Publications
SARS Vaccine
Vaccines Against Newly Emerging Viral Diseases: The Example of SARS
from Bart L. Haagmans writing in Vaccine Design: Innovative Approaches and Novel Strategies
Several newly emerging viral diseases in humans have been reported recently. The ability to identify and characterize the relevant pathogen and develop safe and effective vaccines against these newly emerging pathogens in a timely manner is utmost importance. In this respect, the global response to the SARS epidemic provided valuable experience which can be utilized to respond quickly to future emerging viral infections. In only a few weeks time the nucleotide sequence of this virus was available and through computational analysis of gene sequences diagnostic tests and vaccine candidates were identified and subsequently developed. Eight years after the first SARS outbreak several candidate SARS-CoV vaccines are at various stages of pre-clinical and clinical development. The "classical" inactivated whole virus vaccine as well as a DNA vaccine expressing the spike gene ultimately reached the phase 1 clinical trial testing. These vaccines induce neutralizing antibodies to SARS-CoV and protect against SARS-CoV challenge. However, these vaccines still need to be further tested against viruses closely related to SARS-CoV that potentially may emerge and for the absence of significant side effects. The lessons learned from this outbreak combined with more recently developed techniques may aid the development of effective vaccines against future emerging viral diseases.
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies | Coronaviruses: Molecular and Cellular Biology
from Bart L. Haagmans writing in Vaccine Design: Innovative Approaches and Novel Strategies
Several newly emerging viral diseases in humans have been reported recently. The ability to identify and characterize the relevant pathogen and develop safe and effective vaccines against these newly emerging pathogens in a timely manner is utmost importance. In this respect, the global response to the SARS epidemic provided valuable experience which can be utilized to respond quickly to future emerging viral infections. In only a few weeks time the nucleotide sequence of this virus was available and through computational analysis of gene sequences diagnostic tests and vaccine candidates were identified and subsequently developed. Eight years after the first SARS outbreak several candidate SARS-CoV vaccines are at various stages of pre-clinical and clinical development. The "classical" inactivated whole virus vaccine as well as a DNA vaccine expressing the spike gene ultimately reached the phase 1 clinical trial testing. These vaccines induce neutralizing antibodies to SARS-CoV and protect against SARS-CoV challenge. However, these vaccines still need to be further tested against viruses closely related to SARS-CoV that potentially may emerge and for the absence of significant side effects. The lessons learned from this outbreak combined with more recently developed techniques may aid the development of effective vaccines against future emerging viral diseases.
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies | Coronaviruses: Molecular and Cellular Biology
Streptococcus pneumoniae Vaccine
Vaccines against Streptococcus pneumoniae
from James C. Paton writing in Vaccine Design: Innovative Approaches and Novel Strategies
Existing vaccines against Streptococcus pneumoniae are targeted at the capsular polysaccharide (PS) of which there are 91 distinct serotypes. Polyvalent purified PS vaccines are immunogenic in healthy adults, but not in high risk groups such as young children and the elderly. Development of PS-protein conjugate vaccines has overcome the poor immunogenicity of PS in children, but the protection imparted is strictly serotype-specific, and the number of included serotypes is even more restricted than in the PS vaccine formulations. Widespread introduction of conjugate vaccines in developed countries has dramatically reduced the incidence of invasive pneumococcal disease due to serotypes included in the vaccine. However, these benefits are being eroded by increases in the incidence of disease caused by non-vaccine serotypes. Conjugate vaccines are also expensive, limiting their use in developing countries, where the burden of pneumococcal disease is greatest. Clearly, there is an urgent need to develop alternative pneumococcal vaccines that are (i) inexpensive, (ii) immunogenic in young children, and (iii) provide protection against all pneumococci regardless of serotype. Of particular importance are vaccines comprising pneumococcal proteins that contribute to virulence and are common to all serotypes.
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies | Bacterial Polysaccharides: Current Innovations and Future Trends
from James C. Paton writing in Vaccine Design: Innovative Approaches and Novel Strategies
Existing vaccines against Streptococcus pneumoniae are targeted at the capsular polysaccharide (PS) of which there are 91 distinct serotypes. Polyvalent purified PS vaccines are immunogenic in healthy adults, but not in high risk groups such as young children and the elderly. Development of PS-protein conjugate vaccines has overcome the poor immunogenicity of PS in children, but the protection imparted is strictly serotype-specific, and the number of included serotypes is even more restricted than in the PS vaccine formulations. Widespread introduction of conjugate vaccines in developed countries has dramatically reduced the incidence of invasive pneumococcal disease due to serotypes included in the vaccine. However, these benefits are being eroded by increases in the incidence of disease caused by non-vaccine serotypes. Conjugate vaccines are also expensive, limiting their use in developing countries, where the burden of pneumococcal disease is greatest. Clearly, there is an urgent need to develop alternative pneumococcal vaccines that are (i) inexpensive, (ii) immunogenic in young children, and (iii) provide protection against all pneumococci regardless of serotype. Of particular importance are vaccines comprising pneumococcal proteins that contribute to virulence and are common to all serotypes.
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies | Bacterial Polysaccharides: Current Innovations and Future Trends
Group B Streptococcus Vaccine
Toward the Development of a Universal Vaccine Against Group B Streptococcus
from Roberta Cozzi, John L. Telford and Domenico Maione writing in Vaccine Design: Innovative Approaches and Novel Strategies
Group B Streptococcus (GBS) is one of the most common cause of life-threatening bacterial infections in infants and is also an emerging pathogen among adult humans, especially in the elderly, immunocompromised and diabetic adults. Capsular polysaccharide based vaccines of the most common serotypes present in the United States and Europe are in an advanced stage of development but they are not effective against serotypes present in other parts of the world. Many protein antigens have been studied for the discovery of an effective universal vaccine that could overcome serotype specificity. Thanks to reverse vaccinology and new technologies, a vaccine combination based on the pilus proteins has been discovered for the development of a universal GBS vaccine that is potentially capable of preventing all GBS infections.
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies | Pili and Flagella: Current Research and Future Trends
from Roberta Cozzi, John L. Telford and Domenico Maione writing in Vaccine Design: Innovative Approaches and Novel Strategies
Group B Streptococcus (GBS) is one of the most common cause of life-threatening bacterial infections in infants and is also an emerging pathogen among adult humans, especially in the elderly, immunocompromised and diabetic adults. Capsular polysaccharide based vaccines of the most common serotypes present in the United States and Europe are in an advanced stage of development but they are not effective against serotypes present in other parts of the world. Many protein antigens have been studied for the discovery of an effective universal vaccine that could overcome serotype specificity. Thanks to reverse vaccinology and new technologies, a vaccine combination based on the pilus proteins has been discovered for the development of a universal GBS vaccine that is potentially capable of preventing all GBS infections.
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies | Pili and Flagella: Current Research and Future Trends
Staphylococcus Vaccines
Nosocomial infections: Staphylococcus aureus
from Alice G. Cheng, Olaf Schneewind and Dominique Missiakas writing in Vaccine Design: Innovative Approaches and Novel Strategies
Staphylococcus aureus is the most frequent cause of human skin and soft tissue, bloodstream and respiratory tract infections. Staphylococcal strains have acquired antibiotic resistance traits against available therapies and drug-resistant strains (MRSA, methicillin-resistant S. aureus) are currently isolated in up to 80% of hospital and 60% of community-acquired infections (CA-MRSA). Unlike pneumococci and group A streptococci; S. aureus infections do not raise immunity against subsequent infections. Consistent with this observation, early efforts to develop vaccines from whole-cell killed preparations of staphylococci have failed. More recent work characterized proteins and carbohydrates in the staphylococcal envelope and examined these molecules as protective antigens in vaccine studies. A recent article reviews the pathogenesis of S. aureus infections as well as past and current efforts that have been pursued to develop effective vaccines.
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies | Staphylococcus: Molecular Genetics
from Alice G. Cheng, Olaf Schneewind and Dominique Missiakas writing in Vaccine Design: Innovative Approaches and Novel Strategies
Staphylococcus aureus is the most frequent cause of human skin and soft tissue, bloodstream and respiratory tract infections. Staphylococcal strains have acquired antibiotic resistance traits against available therapies and drug-resistant strains (MRSA, methicillin-resistant S. aureus) are currently isolated in up to 80% of hospital and 60% of community-acquired infections (CA-MRSA). Unlike pneumococci and group A streptococci; S. aureus infections do not raise immunity against subsequent infections. Consistent with this observation, early efforts to develop vaccines from whole-cell killed preparations of staphylococci have failed. More recent work characterized proteins and carbohydrates in the staphylococcal envelope and examined these molecules as protective antigens in vaccine studies. A recent article reviews the pathogenesis of S. aureus infections as well as past and current efforts that have been pursued to develop effective vaccines.
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies | Staphylococcus: Molecular Genetics
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
Detection of Microbial Pathogens
from Jacques Theron, Thomas Eugene Cloete and Michele de Kwaadsteniet in Nanotechnology in Water Treatment Applications
Detection of pathogens often involves time-consuming culture methods. Newer enzymatic, immunological and genetic methods are being developed to replace and/or support classical approaches to microbial detection. Innovations in nanotechnology and nanosciences are having a significant impact in biodiagnostics, where a number of nanoparticle-based assays and nanodevices have been introduced for biomolecular detection.
Waterborne disease is still a major cause of death in many parts of the world, particularly in young children, the elderly, or those with compromised immune systems. As the epidemiology of waterborne diseases is changing, there is a growing global public health concern about new and reemerging infectious diseases that are occurring through a complex interaction of social, economic, evolutionary, and ecological factors. An important challenge is therefore the rapid, specific and sensitive detection of waterborne pathogens.
Further reading: Nanotechnology in Water Treatment Applications
Detection of pathogens often involves time-consuming culture methods. Newer enzymatic, immunological and genetic methods are being developed to replace and/or support classical approaches to microbial detection. Innovations in nanotechnology and nanosciences are having a significant impact in biodiagnostics, where a number of nanoparticle-based assays and nanodevices have been introduced for biomolecular detection.
Waterborne disease is still a major cause of death in many parts of the world, particularly in young children, the elderly, or those with compromised immune systems. As the epidemiology of waterborne diseases is changing, there is a growing global public health concern about new and reemerging infectious diseases that are occurring through a complex interaction of social, economic, evolutionary, and ecological factors. An important challenge is therefore the rapid, specific and sensitive detection of waterborne pathogens.
Further reading: Nanotechnology in Water Treatment Applications