Vibrio cholerae: Genomics and Molecular Biology | Book
Caister Academic Press
Edited by: 1
Shah M. Faruque and 2
G. Balakrish Nair1International Centre for Diarrhoeal Disease Research, Dhaka-1212, Bangladesh and 2National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata - 700 010, India
GB £159 or US $319 (hardback).
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The last decade has witnessed the unravelling of remarkable new insights into the biology of Vibrio cholerae
. These include the discovery of the filamentous phage that encodes cholera toxin, the existence of two chromosomes in V. cholerae
and the sequencing of the whole genome of the V. cholerae
O1 strain N16961. These pioneering works led to an inevitable escalation in the amount of data generate. In this book we have endeavoured to distill the essence of this mighty deluge of information to produce a timely review of the genomics and molecular biology of this important human pathogen.
Written by leading V. cholerae
experts, the chapters review the most important cutting-edge genetic facets of V. cholerae
including its genomic organization, population genetics, molecular epidemiology, and synchronized regulation of gene expression. Other topics include the molecular basis for enhanced transmissibility of cholera during epidemics, survival of the pathogen in the environment, and above all the evolution of the species to attain increased fitness both as a pathogen and an environmental organism. Essential reading for everyone with an interest in Vibrio
and recommended reading for other scientists working in microbial pathogenesis, microbial genomics and antimicrobial research.
"... the current status of molecular genetics of vibrio research ... the extensive introduction is welcome and all the chapters are developed thematically and contain detailed and condensed information" from Biospektrum (2008) 14: 666-667.
"The Editors have recruited leading researchers on cholera biology and therefore the content is up-to-date and authoritative. The reviews are generally useful, timely and well-written ... Would I buy this book? Yes ... " from Microbiology Today (2009) 36: 62.
"... a major strength of this book is that it covers many diverse aspects of V. cholerae ecology, epidemiology, adaptation and evolution. The chapters on genomics and evolution, population genetics and emerging clones present up to date information and relevant references for further exploration of these topics. In addition, there is a chapter on molecular ecology that discusses what is known about the evolution of toxigenic V. cholerae strains and how they survive in the environment, a topic which is extremely timely ... I found this book to be a great resource for describing the current state of the art of V. cholerae molecular biology on a wide range of topics, both medically and environmentally relevant. Thus, this book is valuable reading to anyone involved in the field of cholera research." from
Shah M. Faruque
Dr. Diane McDougald, University of New South Wales, Sydney, Australia writing in Microbe (formerly ASM News)
, the causative agent of cholera belongs to a group of organisms whose natural habitats are the aquatic ecosystems. The strains that cause cholera epidemics have evolved from non-pathogenic progenitor strains by acquisition of virulence genes, and V. cholerae
represents a paradigm for this evolutionary process. Brief description to the virulence genes, their role in pathogenesis, and their possible mode of lateral transfer among different strains have been provided. The genomics and evolution of the species, population structure and multiple factors involved in the distinct epidemiological behaviour of V. cholerae
have also been briefly introduced to make grounds for more detailed description of the topics presented in subsequent chapters.
Genomics of Vibrio cholerae and its Evolution
Elizabeth A. Shakhnovich and Michelle Dziejman
The 4.0 Mbp genome of N16961, an O1 serogroup, El Tor biotype, 7th pandemic strain of V. cholerae
, is comprised of two circular chromosomes of unequal size that are predicted to encode a total of 3,885 genes. The genomic sequence of this representative strain has facilitated global experimental approaches that have furthered our understanding of the genetic and phenotypic diversity found within the species V. cholerae
. Sequence data have been used to identify horizontally acquired sequences, dissect complex regulatory and signaling pathways, and develop computational approaches to predict patterns of gene expression and the presence of metabolic pathway components. In addition, these data have served as a basis for the construction of microarrays to study the evolution of the organism through comparative genomic analyses. Genomic sequencing of additional strains, subtractive hybridization studies and the introduction of new model systems have also contributed to the identification of novel sequences and pathogenic mechanisms associated with other strains. The sequence of strain N16961 has therefore resulted in an expanded view of the genetic repertoire of V. cholerae
and focused our attention on the progressive evolution of this marine bacterium that can also be a human pathogen.
Population Genetics of Vibrio cholerae
Rosario Morales, Gabriela Delgado, and Alejandro Cravioto
The influence of evolutionary forces on the genetic diversity of natural populations of living organisms is the subject matter of population genetics. In the case of Vibrio cholerae
, data obtained from detailed molecular studies of large populations of these bacteria have allowed for a better understanding of the epidemiology of diseases due to their presence in humans. The species has a high genetic diversity and a complex image of its population structure. There is also evidence of linkage disequilibrium and frequent intragenic and assortative recombination events in their housekeeping genes. Horizontal transfer of genes in V. cholerae
is higher than those reported for Escherichia coli
and Salmonella enterica
. In spite of the frequent horizontal gene transfer, clonal lineages of Vibrio cholerae
might persist for decades. The best example of this is the presence and survival of epidemic and pandemic clones over long periods of time. To date, there are four major genetic lines of toxigenic V. cholerae
O1 biotype El Tor: an Australian clone (ET 1); the U.S. Gulf Coast clone (ET 2); the seventh pandemic clone isolated in the South East Asia together with the O139 "Bengal" clone (ET 3); and the clone that caused cholera in Latin America in the 1990's (ET 4). There are also isolated clones that have appeared over time under special conditions, e.g., serogroup O37 that was shown to have limited epidemic potential in the 1960's. Given the close evolutionary relationship between V. cholerae
O1 and other non-O1 virulent serotypes and the fact that virulence genes can be transferred horizontally, new pathogenic strains of V. cholerae
could arise in the future through the modification of existing clones that have the capacity to spread rapidly, and thus cause outbreaks of disease.
Filamentous bacteriophages in Vibrio cholerae genetics and evolution
E. Fidelma Boyd
The role of filamentous phages, particularly CTXΦ in Vibrio cholerae
genetics and evolution are discussed. An overview of the CTXΦ genome structure and interaction with the V. cholerae
host cell during the various stages of the lifecycle of CTXΦ are outlined. The evolution of CTXΦ is explored, and the co-evolution of pIIICTX
and the TcpA, the major pilin protein of TCP the receptor for CTXΦ is examined. Seven diverse filamentous phages have been characterized from V. cholerae
O1 and O139 serogroup isolates and these phages and their putative roles in V. cholerae
biology are reviewed.
Genetics of Vibrio cholerae Colonization and Motility
Brooke A. Jude and Ronald K. Taylor
Survival of Vibrio cholerae
either in the aquatic environment or in the human host is mediated by appropriate expression of factors that control motility, colonization, production of virulence factors, as well as sensing the cell density (quorum sensing). Successful transition of the organism between the aquatic and the host intestinal environments thus depends on the coordinated activity of a number of genes and regulatory circuits. Recent developments in our understanding of the complex gene regulation supporting the cyclic transitions and the dual lifestyle of V. cholerae
has been presented and discussed.
Genetics of O-antigens, Capsules, and the Rugose Variant of Vibrio cholerae
The human pathogen Vibrio cholerae
produces three major cell-surface associated polysaccharides, including (i) lipopolysaccharide (LPS), (ii) capsule, and (iii) rugose exopolysaccharide. While LPS and capsule primarily help the bacterium to evade host defense mechanisms, the rugose exopolysaccharide may aid the bacterium in persisting in the nutrient-deficient aquatic environments. This chapter describes underlying genetic elements and mechanism(s) involved in the biosynthesis and regulation of LPS, capsule and rugose exopolysaccharide elicited by V. cholerae
Genetics and Microbiology of Biofilm Formation by Vibrio cholerae
Fitnat H. Yildiz and Roberto Kolter
In nature, most bacteria grow as matrix-enclosed, surface-associated communities known as biofilms. Vibrio cholerae
, the causative agent of the disease cholera, forms biofilms on diverse surfaces. This ability to form biofilms appears to be critical for the environmental survival and the transmission of V. cholerae
. The molecular mechanisms utilized by V. cholerae
to form and maintain biofilms are being investigated through a combination of molecular genetic and microscopic approaches. A better understanding of the life cycle of this important human pathogen should prove useful in the development of future strategies for predicting and controlling cholera epidemics.
Molecular Ecology of Vibrio cholerae
Shah M. Faruque and John J. Mekalanos
Although Vibrio cholerae
cause human disease, aquatic ecosystems are major habitats of V. cholerae
, and all V. cholerae
are not pathogenic for humans. V. cholerae
represents a paradigm for origination of pathogenic bacteria from environmental nonpathogenic progenitor strains by horizontal transfer of genes. Besides environmental factors which are not precisely defined, bacteriophages, and horizontally transmissible genetic elements have a significant role in the epidemiology and evolution of the pathogen. Recent studies are beginning to reveal the mechanisms associated with the occurrence of seasonal epidemics in endemic areas, water bourn spread of cholera, and the factors that enable the organisms to survive unfavorable conditions in the aquatic environment. The emergence of new epidemic strains, and their enrichment during epidemics of cholera appear to constitute a natural system for the evolution of V. cholerae
and genetic elements that mediate horizontal transfer of genes among bacterial strains.
Coordinated Regulation of Gene Expression in Vibrio cholerae
Rupak K. Bhadra and Bhabatosh Das
, the causative agent of the severe diarrhoeal disease cholera, has evolved with intricate signal transduction and gene regulatory systems to survive and grow under various environmental conditions. The virulence regulon of V. cholerae
, which involves multiple genes working in a coordinated manner, represents a regulatory paradigm for extracellular bacterial pathogens. Availability of the whole genome sequence has allowed microarray based transcriptome analyses of V. cholerae
cells isolated directly from cholera patients. Such studies indicate that quite a large number of genes are involved in the disease process and their expression pattern changes as the infection progresses. Further understanding of the process came with the recent discoveries of small noncoding RNAs and intracellular signal molecule c-di-GMP as modulators of gene expression in V. cholerae
. Transcriptome analysis has also shed light on synchronized gene expression related to chitin utilization and development of natural competence when the organism exists in the natural aquatic environment. Thus, the survival, evolution and pathogenesis of V. cholerae
appear to be controlled by several intricate overlapping regulatory circuits.
Evolutionary Relationships of Pathogenic Clones of Vibrio cholerae
O. Colin Stine
Evolution refers to the differentiation of an ancestral genome into recognizably distinct genomes. Understanding the evolutionary history of an organism can provide insight into how it can be expected to evolve in the future and provide predictions that serve as the basis of where to best focus effort to prevent the emergence of new pathogenic variants. In order to accurately understand the evolutionary history, the methods used for interpreting the genetic variation need to reflect the mechanisms of genetic change. The critical mechanism for deciding how to interpret the genetic relatedness is the amount of recombination. If recombination is rare, then the traditional phylogenetic analysis based on bifurcating trees works well. If recombination is common, then a method that incorporates recombination must be used. Evolutionary relationships among pathogenic clones based on these assessments have been presented and discussed.
Emerging Hybrid Variants of Vibrio cholerae O1
G. Balakrish Nair, Asish K. Mukhopadhyay, Ashrafus Safa and Yoshifumi Takeda
Rapid emergence of genetic variants among toxigenic epidemic strains of Vibrio cholerae
, contributes to the intricate epidemiological pattern of cholera. A remarkable event in recent years has been the emergence of strains of V. cholerae
O1 which possess traits of both the classical and El Tor biotypes. The phenotypic, genetic, and epidemiological characteristics, of these new variants have been reviewed, with particular emphasis on the origin, significance and implications of these strains in the epidemiology of cholera.
Antibiotic Resistance in Vibrio cholerae
Antimicrobial resistance has become a major medical and public health problem as it has direct link with the disease management. Vibrio cholerae
, the cholera causing pathogen is increasingly developing resistance towards many antimicrobials used for the treatment of diarrhoea. However, the pattern of resistance differs from country to country. The well-known factor responsible for development and spread of resistance is injudicious use of antimicrobial agents, which is directly related to the stimulation of several mechanisms of resistance. In V. cholerae
, several resistance mechanisms such as plasmid encoded resistance, mutation in the quinolones resistance determining regions, integrons, efflux pumps and SXT constins have been established. Considering the importance of drug resistance, quick diagnostic assay methods are available for the identification of multidrug resistant (MDR) V. cholerae
. Many new generation antimicrobials were discovered, which are effective against V. cholerae
in the in vitro
studies. The resistance pattern of V. cholerae
to several antimicrobials are not always uniform as it depends on the source of isolation. In some of the recent findings it established that vibrios can act as reservoirs of antimicrobial resistance as cross-spread is common in in vitro
studies. Promotion of indigenous drugs should be considered in the future and studied in detail for their efficacy.
Conclusion and Future Prospect
Shah M. Faruque and John J. Mekalanos
Application of molecular approaches to studying the biology of Vibrio cholerae
, has led to remarkable progress in our general understanding of the genetics, ecology and epidemiology of the pathogen. The bulk of information generated in different areas of V. cholerae
research has been summarized to provide an over all impression of the progress made. Future directions for research into V. cholerae
have also been discussed with a view to understanding general themes of enteric bacterial pathogens, that cause waterborne epidemic diseases.
How to buy this book
(EAN: 9781904455332 Subjects: [bacteriology] [microbiology] [medical microbiology] [molecular microbiology] [genomics])