title: Transcriptional regulators of the GAD acid stress island are carried by effector protein-encoding prophages and indirectly control type III secretion in enterohemorrhagic Escherichia coli O157:H7.
abstract: Type III secretion (T3S) plays a pivotal role in the colonization of ruminant hosts by Enterohemorrhagic Escherichia coli (EHEC). The T3S system translocates effector proteins into host cells to promote bacterial attachment and persistence. The repertoire and variation in prophage regions underpins differences in the pathogenesis and epidemiology of EHEC strains. In this study, we have used a collection of deletions in cryptic prophages and EHEC O157 O-islands to screen for novel regulators of T3S. Using this approach we have identified a family of homologous AraC-like regulators that indirectly repress T3S. These prophage-encoded secretion regulator genes (psr) are found exclusively on prophages and are associated with effector loci and the T3S activating Pch family of regulators. Transcriptional profiling, mutagenesis and DNA binding studies were used to show that these regulators usurp the conserved GAD acid stress resistance system to regulate T3S by increasing the expression of GadE (YhiE) and YhiF and that this regulation follows attachment to bovine epithelial cells. We further demonstrate that PsrA and effectors encoded within cryptic prophage CP933-N are required for persistence in a ruminant model of colonization.
authors.affiliation: Immunity and Infection Division, The Roslin Institute and R(D)SVS, University of Edinburgh, Edinburgh EH25 9RG, UK.
authors.forename: Jai J
authors.initials: JJ
authors.lastname: Tree
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Roe
authors.forename: Allen
authors.initials: A
authors.lastname: Flockhart
authors.forename: Sean P
authors.initials: SP
authors.lastname: McAteer
authors.forename: Xuefang
authors.initials: X
authors.lastname: Xu
authors.forename: Darren
authors.initials: D
authors.lastname: Shaw
authors.forename: Arvind
authors.initials: A
authors.lastname: Mahajan
authors.forename: Scott A
authors.initials: SA
authors.lastname: Beatson
authors.forename: Angus
authors.initials: A
authors.lastname: Best
authors.forename: Sabrina
authors.initials: S
authors.lastname: Lotz
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Woodward
authors.forename: Roberto
authors.initials: R
authors.lastname: La Ragione
authors.forename: Kenan C
authors.initials: KC
authors.lastname: Murphy
authors.forename: John M
authors.initials: JM
authors.lastname: Leong
authors.forename: David L
authors.initials: DL
authors.lastname: Gally
mesh_terms: D000143:Acids / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000382:microbiology*; D004251:DNA Transposable Elements; D004927:Escherichia coli Infections / Q000382:microbiology / Q000662:veterinary*; D019453:Escherichia coli O157 / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000821:virology; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005809:Genes, Regulator; D005968:Glutamate Decarboxylase / Q000235:genetics* / Q000378:metabolism; D039002:Prophages / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D012756:Sheep; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000143:Acids; D004251:DNA Transposable Elements; D029968:Escherichia coli Proteins; D014764:Viral Proteins; D005968:Glutamate Decarboxylase