title: Human neutrophils and their products induce Shiga toxin production by enterohemorrhagic Escherichia coli.
abstract: The Shiga toxins (Stx) are critical virulence factors for Escherichia coli O157:H7 and other serotypes of enterohemorrhagic E. coli (EHEC). These potent toxins are encoded in the genomes of temperate lambdoid bacteriophages. We recently demonstrated that induction of the resident Stx2-encoding prophage in an O157:H7 clinical isolate is required for toxin production by this strain. Since several factors produced by human cells, including hydrogen peroxide (H2O2), are capable of inducing lambdoid prophages, we hypothesized that such molecules might also induce toxin production by EHEC. Here, we studied whether H2O2 and also human neutrophils, an important endogenous source of H2O2, induced Stx2 expression by an EHEC clinical isolate. Both H2O2 and neutrophils were found to augment Stx2 production, raising the possibility that these agents may lead to prophage induction in vivo and thereby contribute to EHEC pathogenesis.
authors.affiliation: Division of Geographic Medicine and Infectious Diseases, New England Medical Center and Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
authors.forename: P L
authors.initials: PL
authors.lastname: Wagner
authors.forename: D W
authors.initials: DW
authors.lastname: Acheson
authors.forename: M K
authors.initials: MK
authors.lastname: Waldor
mesh_terms: D003967:Diarrhea / Q000382:microbiology*; D019453:Escherichia coli O157 / Q000187:drug effects / Q000472:pathogenicity*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018448:Models, Immunological; D009504:Neutrophils / Q000276:immunology*; D022621:Shiga Toxin / Q000096:biosynthesis*; D022641:Shiga Toxin 2 / Q000096:biosynthesis; D017906:Siphoviridae / Q000235:genetics; D014775:Virus Activation
chemical_list: D022641:Shiga Toxin 2; D022621:Shiga Toxin; D006861:Hydrogen Peroxide