期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 103, 期 40, 页码 14941-14946出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0604891103
关键词
bacterial pathogenesis; bacterial protein secretion; bioinformatics; genomics; virulence
资金
- Biotechnology and Biological Sciences Research Council [BB/D010195/1] Funding Source: Medline
- Medical Research Council [G90/80] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
- BBSRC [BB/D010195/1] Funding Source: UKRI
- MRC [G90/80] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/D010195/1] Funding Source: researchfish
- Medical Research Council [G90/80] Funding Source: researchfish
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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