Edinburgh Research Explorer Applying phylogenomics to understand the emergence of Shiga Toxin producing Escherichia coli O157:H7 strains causing severe human disease in the United Kingdom.

: Shiga Toxin producing Escherichia coli (STEC) O157:H7 is a recently emerged zoonotic pathogen with considerable morbidity. Since the serotype emerged in the 1980s, research has focussed on unravelling the evolutionary events from the E. coli O55:H7 ancestor to the contemporaneous globally dispersed strains. In this study the genomes of over 1000 isolates from human clinical cases and cattle, spanning the history of STEC O157:H7 in the United Kingdom were sequenced. Phylogenetic analysis reveals the ancestry, key acquisition events and global context of the strains. Dated phylogenies estimate the time to the most recent common ancestor of the current circulating global clone to 175 years ago, followed by rapid diversification. We show the acquisition of specific virulence determinates occurred relatively recently and coincides with its recent detection in the human population. Using clinical outcome data from 493 cases of STEC O157:H7 we assess the relative risk of severe disease including HUS from each of the defined clades in the population and show the dramatic effect Shiga toxin complement 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 ABSTRACT Shiga Toxin producing Escherichia coli (STEC) O157:H7 is a recently emerged zoonotic pathogen with 26 considerable morbidity. Since the emergence of this serotype in the 1980s, research has focussed 27 on unravelling the evolutionary events from the E. coli O55:H7 ancestor to the contemporaneous 28 globally dispersed strains observed today. In this study the genomes of over one thousand isolates toxin and severe disease. With this analysis we show specific circulating 64 strains have >5 fold increase risk of severe disease than the ancestral STEC O157:H7 genotype. Finally we show that recent strain replacement has occurred in Great Britain shaping the diversity of 66 STEC O157:H7 observed today and introducing a high virulence clone into the British cattle 67 population.

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