An extensive repertoire of type III secretion effectors in Escherichia coli O157 and the role of lambdoid phages in their dissemination

Toru Tobe1, Scott A. Beatson2,3, Hiroyuki Taniguchi4, Hiroyuki Abé1, Christopher M. Bailey3, Amanda Fivian3, Rasha Younis3, Sophie A. Matthews3, Olivier Marchès5, Gad Frankel5, Tetsuya Hayashi6, Mark J. Pallen3
1Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
2School of Molecular and Microbial Sciences, University of Queensland, Brisbane, QLD 4072, Australia
3University of Birmingham Medical School, Birmingham, B15 2TT, United Kingdom;
4Institute of Enzyme Research, University of Tokushima, 3-8-15 Kuramoto, Tokushima 770-8503, Japan;
5Division of Cell and Molecular Biology, Imperial College London, London SW7 2AZ, United Kingdom; and
6**Frontier Science Research Center, University of Miyazaki, 5200 Kiyotake, Miyazaki 899-1692, Japan

Tóm tắt

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.

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