title: An extensive repertoire of type III secretion effectors in Escherichia coli O157 and the role of lambdoid phages in their dissemination.
abstract: Several pathogenic strains of Escherichia coli exploit type III secretion to inject "effector proteins" into human cells, which then subvert eukaryotic cell biology to the bacterium's advantage. We have exploited bioinformatics and experimental approaches to establish that the effector repertoire in the Sakai strain of enterohemorrhagic E. coli (EHEC) O157:H7 is much larger than previously thought. Homology searches led to the identification of >60 putative effector genes. Thirteen of these were judged to be likely pseudogenes, whereas 49 were judged to be potentially functional. In total, 39 proteins were confirmed experimentally as effectors: 31 through proteomics and 28 through translocation assays. At the protein level, the EHEC effector sequences fall into >20 families. The largest family, the NleG family, contains 14 members in the Sakai strain alone. EHEC also harbors functional homologs of effectors from plant pathogens (HopPtoH, HopW, AvrA) and from Shigella (OspD, OspE, OspG), and two additional members of the Map/IpgB family. Genes encoding proven or predicted effectors occur in >20 exchangeable effector loci scattered throughout the chromosome. Crucially, the majority of functional effector genes are encoded by nine exchangeable effector loci that lie within lambdoid prophages. Thus, type III secretion in E. coli is linked to a vast phage "metagenome," acting as a crucible for the evolution of pathogenicity.
authors.affiliation: Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. torutobe@bact.med.osaka-u.ac.jp
authors.forename: Toru
authors.initials: T
authors.lastname: Tobe
authors.forename: Scott A
authors.initials: SA
authors.lastname: Beatson
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Abe
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Bailey
authors.forename: Amanda
authors.initials: A
authors.lastname: Fivian
authors.forename: Rasha
authors.initials: R
authors.lastname: Younis
authors.forename: Sophie
authors.initials: S
authors.lastname: Matthews
authors.forename: Olivier
authors.initials: O
authors.lastname: Marches
authors.forename: Gad
authors.initials: G
authors.lastname: Frankel
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hayashi
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Pallen
mesh_terms: D010582:Bacteriophage lambda / Q000378:metabolism*; D002876:Chromosomes, Bacterial / Q000235:genetics; D019453:Escherichia coli O157 / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D016680:Genome, Bacterial / Q000235:genetics; D006801:Humans; D039002:Prophages / Q000235:genetics; D017385:Sequence Homology; D012760:Shigella / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins