title: Prophage induction is enhanced and required for renal disease and lethality in an EHEC mouse model.
abstract: Enterohemorrhagic Escherichia coli (EHEC), particularly serotype O157:H7, causes hemorrhagic colitis, hemolytic uremic syndrome, and even death. In vitro studies showed that Shiga toxin 2 (Stx2), the primary virulence factor expressed by EDL933 (an O157:H7 strain), is encoded by the 933W prophage. And the bacterial subpopulation in which the 933W prophage is induced is the producer of Stx2. Using the germ-free mouse, we show the essential role 933W induction plays in the virulence of EDL933 infection. An EDL933 derivative with a single mutation in its 933W prophage, resulting specifically in that phage being uninducible, colonizes the intestines, but fails to cause any of the pathological changes seen with the parent strain. Hence, induction of the 933W prophage is the primary event leading to disease from EDL933 infection. We constructed a derivative of EDL933, SIVET, with a biosensor that specifically measures induction of the 933W prophage. Using this biosensor to measure 933W induction in germ-free mice, we found an increase three logs greater than was expected from in vitro results. Since the induced population produces and releases Stx2, this result indicates that an activity in the intestine increases Stx2 production.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Tyler
authors.forename: Karen
authors.initials: K
authors.lastname: Beeri
authors.forename: Jared L
authors.initials: JL
authors.lastname: Reynolds
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Alteri
authors.forename: Katherine G
authors.initials: KG
authors.lastname: Skinner
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Friedman
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Eaton
authors.forename: David I
authors.initials: DI
authors.lastname: Friedman
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D054324:Enterohemorrhagic Escherichia coli / Q000378:metabolism* / Q000821:virology; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000378:metabolism* / Q000401:mortality / Q000821:virology; D007674:Kidney Diseases / Q000378:metabolism* / Q000401:mortality / Q000821:virology; D008136:Longevity; D008297:Male; D051379:Mice; D022641:Shiga Toxin 2 / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D015996:Survival Rate; D016482:Urinalysis; D014775:Virus Activation / Q000502:physiology*
chemical_list: D022641:Shiga Toxin 2
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