Applying phylogenomics to understand the emergence of Shiga-toxin-producing Escherichia coli O157:H7 strains causing severe human disease in the UK

Abstract

Shiga-toxin-producing Escherichia coli (STEC) O157:H7 is a recently emerged zoonotic pathogen with considerable morbidity. Since the emergence of this serotype in the 1980s, research has focussed on unravelling the evolutionary events from the E. coli O55:H7 ancestor to the contemporaneous globally dispersed strains observed today. In this study, the genomes of over 1000 isolates from both human clinical cases and cattle, spanning the history of STEC O157:H7 in the UK, were sequenced. Phylogenetic analysis revealed the ancestry, key acquisition events and global context of the strains. Dated phylogenies estimated the time to evolution of the most recent common ancestor of the current circulating global clone to be 175 years ago. This event was followed by rapid diversification. We show the acquisition of specific virulence determinates has occurred relatively recently and coincides with its recent detection in the human population. We used clinical outcome data from 493 cases of STEC O157:H7 to assess the relative risk of severe disease including haemolytic uraemic syndrome from each of the defined clades in the population and show the dramatic effect Shiga toxin repertoire has on virulence. We describe two strain replacement events that have occurred in the cattle population in the UK over the last 30 years, one resulting in a highly virulent strain that has accounted for the majority of clinical cases in the UK over the last decade. There is a need to understand the selection pressures maintaining Shiga-toxin-encoding bacteriophages in the ruminant reservoir and the study affirms the requirement for close surveillance of this pathogen in both ruminant and human populations.

Shiga Toxin–ProducingEscherichia coliO157, England and Wales, 1983–2012

“…Additionally, outbreaks associated with meat and milk decreased, and outbreaks attributed to petting farms increased. These data support previous reports that PT21/28 is indigenous to Great Britain and PT8 is largely imported, because most PT8 outbreaks were foodborne and a greater proportion of PT21/28 were attributed to environmental or animal contact ( 19 , 21 ). …”

“…In 1996, a new PT was designated PT21/28 after reexamination of the lysis profiles of PT21 and PT28 isolates ( 21 ). By 1996, PT2 (244 [37%] isolates), PT8 (85 [12.9%] isolates), and PT21/28 (92 [13.9%] isolates) were the most common PTs, and the proportion of PT1 (28 [4.2%] isolates) and PT49 (42 [6.4%] isolates) had declined.…”

Support vector machine applied to predict the zoonotic potential of E. coli O157 cattle isolates

“…1A). The pattern for the UK O157 phylogenetic tree is consistent with previous studies (11,13,20) and represents a typical split for UK strains based on lineages: lineage I (n = 140, 70 bovine), II (n = 25, 15 bovine), and I/II (n = 17, 9 bovine). The average number of SNPs within two sequences of the same lineage was 1,859, 379, and 2,190 for lineages I, I/II, and II, respectively.…”

“…The most serious disease in the United Kingdom is associated with lineage I strains and a specific phage type (PT) designated PT21/28; phage typing of UK strains is based on susceptibility testing with a collection of diagnostic bacteriophages (14). The United Kingdom has a high incidence of serious EHEC O157 infections, and the emergence of these infections in the 1990s coincided with the acquisition of the Stx 2a subtype into UK cattle strains already encoding a Stx2c subtype (13,15).…”

“…Within these lineages certain clades predominate, so clade 8 within lineage I/II has been associated in the United States with more serious disease in humans (12). In the United Kingdom, a recent WGS analysis of over 1,000 EHEC O157 human and cattle isolates was used to determine their phylogeny based on core genome SNP analysis (13). The most serious disease in the United Kingdom is associated with lineage I strains and a specific phage type (PT) designated PT21/28; phage typing of UK strains is based on susceptibility testing with a collection of diagnostic bacteriophages (14).…”