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Category: Bacterial Pathogenesis
Population Genetics of Bacteria: a Tribute to Thomas S. Whittam explores the field of bacterial population genetics by highlighting the work of the late Thomas S. Whittam, one of the field’s leading innovators and pioneers. Dr. Whittam helped develop a statistical understanding of the abundance and distribution of genetic diversity within populations of the model organism Escherichia coli. Best known for his work with enterohemorrhagic E. coli O157:H7, a foodborne pathogen, he developed the STEC Center, an acclaimed collection of pathogenic E. coli strains that continues to support the research of clinical scientists, evolutionary biologists, microbiologists, and population geneticists.
Focusing on the application of bacterial population genetics to pathogenic E. coli, this book brings together a compilation of research projects and ideas stemming from Dr. Whittam’s work. Readers gain a broad perspective on the historical development of bacterial population genetics, which underscores how Dr. Whittam’s research has shaped and defined the field. Next, individual contributions examine E. coli from ecological, evolutionary, and clinical perspectives. Finally, the book provides a detailed explanation of how population genetics principles have guided the investigations of the lethal O157:H7 lineage.
Each chapter has been written by one or more leading experts in bacterial population genetics who have been inspired to expand upon the investigations of Dr. Whittam. Readers will discover how the methodologies that Dr. Whittam used to study pathogenic E. coli and O157:H7 now serve as models to investigate many other pathogenic bacterial populations.
Hardcover, 336 pages, color plates, illustrations, index.
This chapter presents the author's interaction with Tom Whittam who had worked on statistical methods and evolutionary biology, and written a review article on Escherichia coli population genetics. Tom's review on the author's manuscript on Helicobacter pylori had suggested the use of the program Reticulate to display homoplasies, i.e., mutations that existed along multiple independent branches of a phylogenetic tree. Based on the suggestions, the author included the output from Reticulate analyses in the revised version, and the paper was accepted by Proceedings of the National Academy of Sciences of the USA, and published later that year. The author says that Tom's insights into phylogenetics in the late 1980s continued to influence how we calculated the ages of clonal lineages until very recently. The calculations used the assumption that a universal clock rate, which was calibrated by the genetic distance between E.coli and Salmonella enterica serovar Typhimurium and an estimated time of separation of 160 million years, could be applied to date the coalescent of a clonal lineage. This clock rate was used to calculate that the Mycobacterium tuberculosis complex evolved 20,000 years ago and that the E.coli O157:H7 lineage evolved from O55:H7 some 40,000 years ago. The author concludes that Tom was one of the few early founders of modern bacterial population genetics and has left a lasting impression on the field, particularly so on those who met him.
In this chapter, the author considers the origins and early history of the enterprise: population genetics, genetic epidemiology, evolutionary genetics, molecular epidemiology, molecular evolution, molecular phylogeny, or molecular forensics, to which Tom Whittam made his awesome contributions. Tom was one of the first to apply population genetics procedures and theory to the genetic epidemiology of bacteria from clinical and other natural sources. From a population genetics perspective, the result of our E. coli enzyme variation study and its interpretation had sufficient “man bites dog” appeal to appear in Science. On the other hand, neither the considerable variability nor the clonal population genetic structure would have been surprising to microbiologists studying the epidemiology of bacteria from clinical and natural sources. Similar observations were made for a number of different species of bacteria with serological as well as other phenotypic markers, like phage resistance patterns (phage typing), repertoires of fermentation capabilities (biotyping), and the distribution of plasmids carried (plasmid typing). By the early 1980s investigators studying the genetic epidemiology of bacteria were also beginning to use various kinds of restriction endonuclease cutting procedures for these epidemiological studies. The author believes that the single most important consequence of early- 1980s studies of genetic variation in E. coli was not direct genetic evidence for the clonal structure of E. coli, which the enzyme data provided, but rather the introduction of population genetics theory and approaches to the genetic epidemiology of bacteria.
The concept of clone is fundamental to the study of prokaryotic evolution and is the essential starting point for any discussion on horizontal genetic exchange. Neisseria and Campylobacter share the property of being accidental pathogens—in that they cause human disease as a consequence of dysfunctional or accidental associations with humans—but the disease syndromes that they cause are very different. Neisseria and Campylobacter populations are, however, similarly structured, both exhibiting extensive evidence of frequent horizontal genetic exchange. In the case of Neisseria, the phenotype of interest is the proclivity of certain genotypes to cause invasive disease, which is apparently paradoxical in organisms that have evolved to colonize humans asymptomatically. In the case of Campylobacter, the question relates to the genetic bases of the association of particular genotypes with different animal species. This chapter talks about the impact that studies of the population biology of these genera have had on our understanding of the bacterial species concept. Horizontal genetic exchange has recently become central to discussion of bacterial species and speciation, although there remains much argument concerning the nature of bacterial species and the means whereby they arise and are maintained. In many species, including N. meningitidis and C. coli, bacterial populations show structuring, with evidence for some clonal signal notwithstanding high rates of recombination. Multilocus sequence typing (MLST) studies have substantially advanced our understanding of the population biology and evolution of many pathogenic bacteria and an increasing number of bacteria that are not pathogens of humans.
The primary motivation for the switch from generating sequence data to analyzing sequence data was the pace at which genomic information became available, and this chapter focuses on a few of the findings that emerged from the comparative genomics of E. coli. Based on disease potential in humans, E. coli strains can be broadly classified as (i) harmless commensals, (ii) intestinal pathogens, and (iii) those capable of infecting extraintestinal sites. An active region of genome evolution is the mutS-rpoS intergenic region. Both the mutS and rpoS genes are highly conserved among strains, but the intergenic region between them can vary from 9.8 kb in some enteropathogenic E. coli (EPEC) strains to 6.9 kb in K-12 and some extraintestinal pathogenic E. coli (ExPEC) strains to 3.7 kb in O157:H7 strains. The polymorphism in this genomic segment is likely related to the high frequency of mutations observed in both mutS and rpoS. In addition to the substantial role that gene acquisition has played in the evolution and formation of pathogenic lineages, mutations that alter or abolish protein functions have also been implicated in the accelerated adaptation of E. coli to diverse environments. The most extensive study of E. coli comparative genomics to date includes 20 E. coli/Shigella strains and one Escherichia fergusonii strain. In summary, the genomes of E. coli and other bacteria have been influenced by numerous factors, but in the case of their overall size and complexity, nonadaptive processes, such as mutation and genetic drift, appear to be more important.
This chapter briefly summarizes the most important differences in genetic exchange. In bacteria, genetic exchange is unidirectional, where a usually small chromosomal segment transfers from a donor to a recipient. Bacterial recombination can occur across vastly more divergent organisms than is possible in animals and plants. The chapter also talks about the challenge of identifying ecotypes, or bacterial species subjected to intrapopulation cohesion provided by periodic selection and/or drift. The Recurrent Niche Invasion model takes into account the role of mobile genetic elements, such as plasmids or phage, in determining bacterial niches. Recombination does not seem likely to be a cohesive force that quashes speciation in either the macroorganisms or bacteria. Most clearly in bacteria, recombination is not sufficient to prevent adaptive divergence in niche-specifying genes, and sexual isolation is not required for bacterial speciation. Studies of speciation in bacteria have focused on the origins of niche-specifying adaptations that distinguish newly divergent species, by investigating the ecological dimensions of speciation and the roles of horizontal genetic transfer and homologous recombination in bacterial speciation. This emphasis on the origins of ecological divergence was forced on bacteriology because bacteria can acquire niche-transcending genes potentially from any organism; so it would be futile to study the end of sharing niche-transcending adaptations in bacteria. It appears that, fortuitously, bacteriology has produced a paradigm of value for species studies in macroorganisms as well as bacteria—that our focus should be on the origins of ecological diversity and not on barriers to recombination.
This chapter presents an overview of the habitats where Escherichia coli can be isolated. It reviews some of the data that characterize the boundaries of its broad ecological niche. The genus Escherichia is not as genetically diverse as once thought and contains only three named species: E. albertii, E. fergusonii, and E. coli. The frequency of gene flow among the phylogenetic lineages and the phylogenetic scale at which it is occurring suggest that boundaries to gene flow among Escherichia species are minimal and also that clades may not occupy entirely different ecological niches. The chapter discusses the niche of E. coli . A human host typically harbors two or three genotypes, and together these genotypes represent the majority of the E. coli cells to be found in a sample. First, nine or more genotypes may be detected in a sample at a single point in time. Second, selective plating reveals the presence of genotypes that exist at very low frequencies. Finally, the number of samples that contain rare genotypes also indicates that there may be a rather large pool of genotypes. The high densities of E. coli in sand led many to speculate that, as in the tropics and subtropics, E. coli is an environmental organism even in some of the coldest temperate regions. E. coli is widespread among warm-blooded animals and humans, and the dynamics of its colonization of the gastrointestinal (GI) tract is dependent on a number of host and microbial determinants.
The strains of E. coli that cause such extraintestinal infection, in whatever host species, have long been recognized to differ, collectively, from those that colonize the intestinal tract or cause diarrhea in members of the same species. Such strains have been the subject of considerable study in an effort to better understand their distinguishing features, virulence mechanisms, host and syndrome range, evolutionary origins, reservoirs, and transmission pathways. This has led to the creation of various taxonomic categories and commensals. Such labels imply that the special ability of these strains to cause extraintestinal disease is their raison d'être. Several broad generalizations can be made regarding the distribution of virulence factors among individual extraintestinal pathogenic E. coli (ExPEC) strains. First, ExPEC strains typically express representatives of multiple different functional categories of virulence factors. Second, ExPEC strains commonly display multiple representatives of a particular functional class of virulence factors. Third, different ExPEC strains exhibit radically different combinations of virulence factors, evidence that multiple E. coli genotypes can cause extraintestinal virulence. An important aspect of virulence genes, aside from presence/absence and expression, is point mutations. In contrast, pulsed-field gel electrophoresis (PFGE) analysis, which is relatively insensitive to broad phylogenetic relationships, provides resolution down to the level of individual clones within the larger clonal groups. Better understandings of ExPEC strains’ pathogenetic mechanisms, fecal reservoirs, transmission pathways, antimicrobial resistance development, and evolutionary origins are needed to guide the development of effective preventive measures against these important opportunistic pathogens.
Shiga toxin-producing Escherichia coli (STEC) is an important food-borne pathogen that can cause nonbloody diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome(HUS). The first isolation of shiga toxin-producing Escherichia coli (STEC) O157 from cattle occurred in Argentina in 1977, when three E. coli O157 strains were recovered from feces of 13 calves aged 1 to 3 weeks with colibacillosis in Buenos Aires Province. In a study on STEC carriage in feedlots, four STEC O157 strains harbored the stx 2, eae, ehxA genes. In this study the prevalence of non-O157 STEC strains was 45.2%. In a study that analyzed fecal samples from steers at slaughter in order to evaluate two PCR procedures for STEC detection, non-O157 STEC strains were isolated from 15.8% of calves with diarrhea, with a majority of strains (60%) carrying the stx1 gene. With respect to the routes of contamination of the carcasses with non-O157 STEC serotypes, the study showed that identical serotypes were recovered in carcasses and feces of the same animal in 4% (3/73) of the cases. STEC strains are widespread in Argentina, and infect humans and animals and contaminate food products. Postenteric HUS is endemic, with more than 500 cases reported each year. Different serotypes and genotypes are detected, and the severity of clinical symptoms caused by STEC has been associated with its virulence profile, especially the stx genotype.
Shigella and enteroinvasive Escherichia coli (EIEC) are a class of enteric pathogens that have evolved the ability to invade epithelial cells and cause severe intestinal illness. In a study on evolutionary analysis of Shigella at the DNA sequence level, the nucleotide sequence of 7,160 bp representing eight housekeeping loci from four regions of the genome was determined. Polymerase chain reaction (PCR) amplification of three marker loci was used to screen for SHI-4, which appeared to be widespread among the clonal groups. Since the isolates used in a study on molecular epidemiology of the Shigella island 4 (SHI-4) PAI were selected on the basis of resistance to multiple antibiotics, it is possible that the actual distribution of these loci among Shigella and EIEC may be different in a randomly sampled collection of strains. Other reports of gene acquisition stem from comparisons of available genome sequences. In contrast to gene acquisition, there is growing evidence that gene loss has been important in the adaptive radiation of Shigella and EIEC. Both gene acquisition and loss have played a major role in the adaptation of these radiations; selection has favored both the establishment of certain virulence factors in particular lineages and the independent deletion of antivirulence functions.
The size of sequenced Escherichia coli genomes varies from 4.6 Mb for the fecal/commensal E. coli K-12 strain MG1655 to 5.5 Mb for enterohemorrhagic E. coli (EHEC) strain O157:H7 EDL933. The majority of these differences are attributed to the insertion of large regions of genomic DNA. This chapter examines genes present on genomic islands and islets of uropathogenic E. coli (UPEC), with a primary focus on genes contributing to the overall fitness of the organism rather than traditional virulence genes. The acquisition and stable integration of multiple genomic islands and islets encoding fimbrial adhesins in UPEC illustrate the significance of adhesion within the urinary tract. The abundance of horizontally acquired, coregulated fimbrial adhesins in UPEC, each with distinct adhesive moieties, demonstrates a clear functional redundancy. The authors identified the sit iron transport system in six of seven arbitrarily selected UPEC strains and only one of three fecal/commensal strains (not in E. coli K-12) using CGH. Several well-studied E. coli strains, ABU strain 83972 and E. coli Nissle 1917, may hold the key to understanding their pathogenic E. coli relatives. ABU strain 83972 has lost many of the typical UPEC virulence genes and yet has retained systems contributing to fitness, particularly those involved in iron acquisition and transport (aerobactin, salmochelin, yersiniabactin, heme/hemoglobin, and sitABCD).
This chapter focuses on study of Escherichia coli evolution, and examines what is understood concerning the diversity of this highly heterogeneous pathovar, recent insights from whole and partial genome sequences, and how these data may eventually be used to further clarify what factors make enteroaggregative E. coli (EAEC) pathogens. In 1999, a collaborative effort between Tom Whittam’s lab and Jim Nataro’s lab provided the first large-scale phylogenetic determination of a worldwide collection of EAEC isolates, as well as isolates previously identified as diffusely adherent E. coli (DAEC). In this study, isolates were screened by 20-locus multilocus enzyme electrophoresis (MLEE) as well as colony hybridizations to 10 plasmid-and chromosome-encoded virulence genes. These results provided for the first time a more complete picture of EAEC diversity, and several important points came to light. First, three phylogenetic groups containing EAEC strains were identified and designated EAEC1, EAEC2, and AA/DA. Second, even in cases where DAEC and EAEC strains intermingled within the same phylogenetic group, these strains were clearly distinguished by the fact that DAEC did not carry EAEC virulence determinants. Third, a few strains were classified as EAEC by the HEp-2 adherence assay but were DNA probe negative for all the screened EAEC virulence factors and clustered phylogenetically outside of EAEC1, EAEC2, and AA/DA. To date, two complete and one shotgun-assembled EAEC genome sequences are available, providing important data for comparative studies between typical and atypical EAEC, as well as EAEC from different phylogenetic groups.
This chapter discusses the emergence and impact of shiga toxin-producing Escherichia coli (STEC) in human disease, the biology of the Shiga toxins (Stx) family, and approaches to diagnosis, treatment, and prevention of infection with STEC. The occurrence of the seminal STEC outbreaks highlighted the need to implement laboratory methods to readily detect E. coli O157:H7. Although early characterization of STEC strains was made possible by Whittam’s multilocus enzyme electrophoresis (MLEE) method, genetic techniques now allow comparison of strains at the nucleotide level. The current model of the predominant pathway by which Stx intoxicates sensitive cells is as follows: (i) the B pentamer of holotoxin binds to Gb3 within lipid rafts; (ii) the entire receptor-holotoxin complex is endocytosed; (iii) the complex moves by retrograde transport to the Golgi and then to the endoplasmic reticulum; and (iv) the A1 subunit is released into the cytoplasm, where it targets the ribosome. Although transduction of stx genes into E. coli via bacteriophages was crucial to the emergence of STEC, the biology of these toxin-converting phages also contributes significantly to the degree of toxin expression and hence the virulence exhibited by STEC. Although the pathogenicity of various STEC strains that synthesize different types of Stx2 cannot be compared directly because the strains are not isogenic, the authors have found that an O91 strain that produces Stx2 is not virulent in the streptomycin-treated mouse model for STEC infection, whereas O91 strains that produce Stx2d-activatable are highly virulent in those mice.
The first model for the evolution of Escherichia coli O157:H7 was proposed over a decade ago. This model was based on data from multilocus enzyme electrophoresis, sorbitol fermentation, β-glucuronidase activity, and the presence/absence of the genes encoding the two main antigenic forms of Shiga toxin (Stx): stx1 and stx2. With the higher-resolution, single nucleotide polymorphisms (SNPs)-based phylogenetic framework in place, the stepwise model can be expanded further through the examination of the Stx profiles present within the clades. With clade 7a, the model once again bifurcates with one line losing stx1 (clade 7b) and the other evolving into clade 5a. The observed changes in the tolA locus emphasize the utility of the revised model to elucidate the complex relationships among otherwise closely related isolates. The updated stepwise evolution model highlights the dynamic nature of the phage-encoded Stx variants, as each was independently acquired and lost multiple times during the diversification of O157:H7. Finally, this model reflects a collective effort on the part of multiple investigators to describe the nature, population genetic diversity, and emergence of pathogenic bacteria.
This chapter reviews the findings on some of atypical strains, examines the genetic mutations underlying their atypical phenotypes, addresses the impact they have on public health, and discusses how they fit into the evolutionary model of Escherichia coli O157:H7. Almost all generic E. coli strains produce β-glucuronidase (GUD), so a popular assay to identify E. coli utilizes the fluorogenic GUD substrate 4-methylumbelliferyl-β-D-glucuronide. The definitive identification of O157:H7 strains is based on the serological presence of both the O and the H antigens. The authors found that the majority of Shiga toxin (Stxs)-producing O157:NM strains are actually phenotypic variants of O157:H7 and they can sometimes be induced to express the H7 antigen. More recent analysis by multilocus sequence typing (MLST) concurred with the multilocus enzyme electrophoresis (MLEE) results in that both TT12A and TT12B had ST66, the most common genotype for O157:H7 strains. The somatic (O) 157 and the flagellar (H) 7 antigens are key markers that are extensively used in diagnostics to identify the O157:H7 serotype. Many of the atypical O157:H7 variants have a public health impact, as they are often pathogenic and will cause illness but, due to the lack of trait marker(s), are not easily detected by assays routinely used to test for O157:H7. Although phenotypically distinct, many of the atypical O157:H7 variants were found to have identical multilocus genotypes (ST66) and belong to the A6 clonal group. Therefore, such strains represent newly identified O157:H7 variants that merely lost typical phenotypic features.
This chapter reviews the impact of Tom's contributions to the field of microbial evolution and to the evolution of one's understanding of the enteric pathogenicity of E. coli. Additional progress was made, also in Germany, in the 1920s: Adam demonstrated groups of E. coli that were biochemically distinct, which he termed ‘’dyspepsiekoli’’. The resulting genetic analysis categorized the species into four main groups (A, B1, B2, and D) and one minor group (E), and generated a widely used phylogenetic reference that has served as the foundation for investigators in the generation since. The putative cardinal virulence trait of E. coli O157:H7, namely, the possession of one or more Shiga toxin genes, was not by itself sufficient to cause severe human disease. The author says that Tom also identified different eae (intimin) alleles as different classes of EPEC and Shiga toxin-producing E. coli (STEC) were described, and framed his work in the context of microbial evolution, epidemiology, and clinical medicine. Despite these limitations, Tom expounded graciously and patiently on his theories of clonality. Tom's investigations into the emergence of diarrheagenic E. coli, and most particularly of the O157:H7 EHEC 1 clade, stand as monumental and enduring contributions to the field.
A relative of enterohemorrhagic Escherichia coli (EHEC) O157:H7, namely, sorbitol-fermenting (SF) E. coli O157:H- (nonmotile), is an important and fascinating human pathogen. The author highlights that researchers were quite motivated to find the infecting pathogen, because the PCR with primers MK1/MK2 from the enrichment culture was positive, the sorbitol MacConkey (SMAC) agar results not withstanding. Therefore, these researchers performed a colony blot hybridization test. The colonies identified with this procedure agglutinated in anti-O157 serum. Because of their ability to ferment sorbitol after overnight incubation, SF EHEC O157:H- strains cannot be distinguished from the physiological intestinal microflora using SMAC agar. This medium remains the most commonly used, rapid, and appropriate way to isolate EHEC O157:H7. At the beginning of the 1990s, researchers sought to identify virulence factors of SF EHEC O157:H- and to determine whether or not these strains were only slight phenotypic variants of non-sorbitol-fermenting (NSF) EHEC O157:H7 or if they were substantially different. They formulated an evolutionary model that includes several steps in the emergence of E. coli O157:H7. EHEC O157:H7 and SF EHEC O157:H- differ in several important aspects, including their phenotypes, the epidemiology of the infection, and the risk of the progression of the infection to hemolytic uremic syndrome (HUS).
Tom Whittam's pioneering research into the structure of Escherichia coli populations not only advanced the field of microbial evolution and genetics, but it also provided a contextual framework for investigating variation in the epidemiology and virulence of bacterial populations. This chapter highlights the work of his laboratory involving the use of various population genetic strategies for characterizing E. coli pathotypes, particularly enterohemorrhagic E. coli (EHEC) O157:H7, while focusing on contributions to epidemiology and public health. To determine whether specific genotypes are associated with human enteric disease, multilocus enzyme electrophoresis (MLEE) was used to examine 1,300 E. coli strains representing 16 serotypes, including EHEC O157:H7 from patients with hemorrhagic colitis and hemolytic uremic syndrome (HUS). Similar to MLEE and multilocus sequence typing (MLST) data, systematic analysis of single nucleotide polymorphisms (SNPs) is amenable to both population genetic and phylogenetic analyses. SNPs data can also be used to examine epidemiological associations between bacterial genotypes and clinical disease. By using the SNP genotyping phylogeny as a framework, it is possible to investigate virulence gene diversity, allelic variation, and gene expression differences among genotypes to identify bacterial genomic determinants of colonization, pathogenesis, and transmissibility. The chapter describes differences in stress resistance properties among clades, nonrandom distribution of stx variants, variation in adherence to epithelial cells, and differential expression among shared genes.
This chapter identifies epidemiologic and ecologic factors within the animal reservoir that are insufficiently understood but which may offer potential for control of Escherichia coli O157:H7. O157:H7 has been isolated from a diverse set of animal host species, in which it generally is not associated with any clinical abnormalities. The chapter describes the role of the reservoir in the epidemiology of zoonotic O157:H7 infections, and discusses evolution of O157:H7 and the animal reservoir. Considerable emphasis has been placed on characterizing O157:H7 colonization of domestic ruminants, particularly cattle and sheep, compared to other host species due to their prominence as sources of human infection. This work has included prevalence; descriptive epidemiology of O157:H7 shedding; identifying farm management factors associated with high prevalence of animal infection; and investigating the effects of vaccines, probiotics, and other interventions. Seasonal variation of O157:H7 fecal shedding by cattle has been reported in geographically diverse regions. There is little evidence that O157:H7 is a ‘‘professional pathogen’’; rather, it is a well-adapted commensal of numerous animal hosts. It has considerable strain diversity within cattle, and only a subset of strains is strongly associated with human disease. As the agent first came to human attention due to the severity of disease, it is natural that research attention has been primarily focused on pathogenesis.
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Quarterly Review of Biology
The book represents a compilation of chapters on the topics that one way or another were the focus of research of a recently and untimely departed Thomas S. Whittam—a great scientist and individual who had been one of founders of and undisputed leaders in the modern bacterial population genetics and molecular epidemiology. There are 18 chapters contributed by top experts in the field around the globe (from ten different countries). The broad range of topics are organized into four sections, covering general concepts of microbial evolution, molecular epidemiology, bacterial virulence, and ecology. With exception of the chaptersin the first, general section, the book is centered around Escherichia coli, in particular extraintestinal(ExPEC), enteroaggregative (EAEC), shiga toxinproducing(STEC) and, to the greatest extent, enterohemorrhagic(EHEC) pathotypes of the species. However, an informative chapter on Neisseria and Campylobacter is presented as well.
Overall, the contributions are of exceptional quality, certainly a great reflection on the legacy left by Whittam. Many chapters are devoted to the role of horizontal gene transfer on the population structure and dynamics of the E. coli pathogens and bacterial species overall. Ample genomic evidence is presented to illustrate how gene transfer shapes the evolution of pathotypes. Throughout the volume, the topic of natural ecology of pathogenic E. coli—one of the biggest passions of Whittam — can be clearly traced. How do pathogens emerge? What drives their continuous circulation in nature? What are the molecular epidemiology tools that can be used to track them? These and many other important questions are posed and well answered in the book. Virtually every chapter outlines the great contributions made in the field and individual subfields by Whittam, making this volume a true tribute to him.
This book will be very informative for a wide audience—population biologists, molecular epidemiologists, and ecology/evolution instructors, as well as graduate students.
Quarterly Review of Biology
Reviewer: Evgeni V. Sokurenko, Microbiology, University of Washington, Seattle, Washington
Review Date: June 2013
This is an excellent book, celebrating Thomas Whittam who died in his prime as a key contributor to understanding of the biology of our most important model bacterium. However only 4 of 18 chapters really reflect the title. There is very little digression towards the broader landscape of bacterial diversity in the context of population genetics and evolution. It is largely a wide-ranging compendium of authoritative reviews of the biology of Escherichia coli, with a slant towards evolutionary and population biology with Whittam's contributions to the field in mind, but with much else besides. There is a focus on E. coli as a pathogen, but its wider existence in the environment and as a commensal organism in the digestive tract - the 'niche' - is also reviewed. I recommend the book unreservedly to anyone interested in the broader biology of E. coli and it should be available in any institution where microbiology is taught.
Society for General Microbiology - Microbiology Today
Reviewer: Charles Penn, University of Birmingham
Review Date: August 2012