title: Applying phylogenomics to understand the emergence of Shiga-toxin-producingEscherichia coliO157:H7 strains causing severe human disease in the UK.
abstract: Shiga-toxin-producingEscherichia 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 theE. coliO55: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.
authors.affiliation: Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Dallman
authors.affiliation: Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Ashton
authors.affiliation: Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: Byrne
authors.affiliation: Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Neil T
authors.initials: NT
authors.lastname: Perry
authors.affiliation: Animal Laboratories and Plant Health Agency, Woodham Lane, Surrey KT15 3NB, UK.
authors.forename: Liljana
authors.initials: L
authors.lastname: Petrovska
authors.affiliation: Animal Laboratories and Plant Health Agency, Woodham Lane, Surrey KT15 3NB, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Ellis
authors.affiliation: Scottish E. coli O157/VTEC Reference Laboratory, Department of Laboratory Medicine, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, UK.
authors.forename: Lesley
authors.initials: L
authors.lastname: Allison
authors.affiliation: Scottish E. coli O157/VTEC Reference Laboratory, Department of Laboratory Medicine, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, UK.
authors.forename: Mary
authors.initials: M
authors.lastname: Hanson
authors.affiliation: Scottish E. coli O157/VTEC Reference Laboratory, Department of Laboratory Medicine, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Holmes
authors.affiliation: Future Farming Systems, R&D Division, SRUC, Drummondhill, Stratherrick Rd., Inverness IV2 4JZ, Scotland, UK.
authors.forename: George J
authors.initials: GJ
authors.lastname: Gunn
authors.affiliation: Centre for Immunity, Infection and Evolution, Kings Buildings, University of Edinburgh, Edinburgh EH9 3FL, UK.
authors.forename: Margo E
authors.initials: ME
authors.lastname: Chase-Topping
authors.affiliation: Centre for Immunity, Infection and Evolution, Kings Buildings, University of Edinburgh, Edinburgh EH9 3FL, UK.
authors.forename: Mark E J
authors.initials: MEJ
authors.lastname: Woolhouse
authors.affiliation: Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Kathie A
authors.initials: KA
authors.lastname: Grant
authors.affiliation: Division of Infection and Immunity, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin EH25 9RG, UK.
authors.forename: David L
authors.initials: DL
authors.lastname: Gally
authors.affiliation: University of East Anglia, Norwich NR4 7TJ, UK.
authors.forename: John
authors.initials: J
authors.lastname: Wain
authors.affiliation: Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Jenkins
keywords: Escherichia coli; One Health; Shiga toxin; emerging infections; genomics; public health microbiology