Chapter 15 : Thomas Whittam, Shiga Toxin-Producing , and the Clinical Consequences of Clonality

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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 . Additional progress was made, also in Germany, in the 1920s: Adam demonstrated groups of 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 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 (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 , and most particularly of the O157:H7 EHEC 1 clade, stand as monumental and enduring contributions to the field.

Citation: Leopold S, Tarr P. 2011. Thomas Whittam, Shiga Toxin-Producing , and the Clinical Consequences of Clonality, p 257-272. In Walk S, Feng P (ed), Population Genetics of Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555817114.ch15

Key Concept Ranking

Bacterial Genetics
Microbial Pathogenesis
Microbial Evolution
Hemolytic Uremic Syndrome
Single Nucleotide Polymorphism
Escherichia coli
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Image of Figure 1.
Figure 1.

Early presentation on EHEC by Tom Whittam. (Left) Abstract book cover. (Right) Abstract of talk delivered by Tom Whittam on the afternoon of Tuesday, July 14, 1987.

Citation: Leopold S, Tarr P. 2011. Thomas Whittam, Shiga Toxin-Producing , and the Clinical Consequences of Clonality, p 257-272. In Walk S, Feng P (ed), Population Genetics of Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555817114.ch15
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Image of Figure 2.
Figure 2.

Unexplained faint band in a gel. Primers within in O55:H7 produced a prominent 340-bp amplicon (white oval) as expected because this gene is not disrupted by a bacteriophage. Primers across the same site in as well as O157:H7 yield fainter bands (black oval), whereas we anticipated a stronger band, as in the nontoxigenic progenitor strain, O55:H7, amplified using the same primer set. Subsequent work demonstrated that a truncated bacteriophage occupied this site in O157:H7 that did not contain (black dashed oval); the bacteriophage-chromosome junction amplicons are within the white dashed borders. Additional amplifications led us to deduce the precise phylogeny of emergence of the three major O157: H7 subgroups ( ). These data eventually led us to formulate a precise emergence of the EHEC 1 clade (see Fig. 3 ). Reproduced with permission from Fig. 1 in reference .

Citation: Leopold S, Tarr P. 2011. Thomas Whittam, Shiga Toxin-Producing , and the Clinical Consequences of Clonality, p 257-272. In Walk S, Feng P (ed), Population Genetics of Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555817114.ch15
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Image of Figure 3.
Figure 3.

Evolutionary scenario for EHEC 1 pathogens. O55:H7 belongs to the most ancestral subgroup (A) of the EHEC 1 clade. The second sphere from the left (lower row) depicts a probably extinct intermediate between O55:H7 and expressing the O157 lipopolysaccharide (LPS), with subgroup B consisting of the sorbitol-fermenting O157:H and subgroup C consisting of O157:H7. We note several critical intraclade events. The ovals within clusters represent genomically sequenced strains (middle gray). Strains used for single nucleotide polymorphism (SNP) consensus sampling are black, inferred founders are light gray, and postulated organisms that are immediate progenitors to the next cluster or subgroup are white ovals. In cluster 1, screened strains were assigned to the main branch if they had each of the three signature SNPs among the 111 shared SNPs ( / ), and the minor branch if they lacked this set of SNPs ( / ). More extensive evolutionary detail is provided in Fig. S1 in reference . Distances not drawn to scale. Reprinted with permission from reference . GUD, β--glucuronidase; TAI, tellurite resistance- and adherence-conferring island.

Citation: Leopold S, Tarr P. 2011. Thomas Whittam, Shiga Toxin-Producing , and the Clinical Consequences of Clonality, p 257-272. In Walk S, Feng P (ed), Population Genetics of Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555817114.ch15
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