title: Shiga toxin 2a and Enteroaggregative Escherichia coli--a deadly combination.
abstract: In 2011, a Shiga toxin (Stx) type 2a-producing enteroaggregative E. coli (EAEC) strain of serotype O104:H4 caused a large lethal outbreak in Northern Europe. Until recently, the pathogenic mechanisms explaining the high virulence of the strain have remained unclear. Our laboratories have shown that EAEC genes encoded on the pAA virulence plasmid, particularly the AggR-regulated AAF/I fimbriae, enhance inflammation and enable the outbreak strain to both adhere to epithelial cells and translocate Stx2a across the intestinal epithelium, possibly explaining the high incidence of the life threatening post-diarrheal sequelae of hemolytic uremic syndrome. Epidemiologic evidence supports a model of EAEC pathogenesis comprising the concerted action of multiple virulence factors along with induction of inflammation. Here, we suggest a model for the pathogenesis of the O104:H4 outbreak strain that includes contributions from EAEC alone, but incorporating additional injury induced by Stx2a.
authors.affiliation: a Statens Serum Institut; Department of Microbiology and Clinical Control ; Copenhagen , Denmark.
authors.forename: Nadia
authors.initials: N
authors.lastname: Boisen
authors.forename: Angela R
authors.initials: AR
authors.lastname: Melton-Celsa
authors.forename: Flemming
authors.initials: F
authors.lastname: Scheutz
authors.forename: Alison D
authors.initials: AD
authors.lastname: O'Brien
authors.forename: James P
authors.initials: JP
authors.lastname: Nataro
mesh_terms: D000818:Animals; D004196:Disease Outbreaks; D004926:Escherichia coli / Q000235:genetics* / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000453:epidemiology* / Q000382:microbiology / Q000473:pathology*; D005060:Europe / Q000453:epidemiology; D006801:Humans; D008954:Models, Biological; D010957:Plasmids; D022641:Shiga Toxin 2 / Q000235:genetics*
chemical_list: D022641:Shiga Toxin 2
keywords: Mechanisms of pathogenesis of gut microbes; O104:H4; Shiga toxin; diarrhea; enteroaggregative Escherichia coli (EAEC); virulence