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

被引:357
作者
Tobe, Toru
Beatson, Scott A.
Taniguchi, Hisaaki
Abe, Hiroyuki
Bailey, Christopher M.
Fivian, Amanda
Younis, Rasha
Matthews, Sophie
Marches, Olivier
Frankel, Gad
Hayashi, Tetsuya
Pallen, Mark J.
机构
[1] Osaka Univ, Grad Sch Med, Suita, Osaka 5650871, Japan
[2] Univ Birmingham, Sch Med, Birmingham B15 2TT, W Midlands, England
[3] Univ Queensland, Sch Mol & Microbial Sci, Brisbane, Qld 4072, Australia
[4] Univ Tokushima, Inst Enzyme Res, Tokushima 7008503, Japan
[5] Univ London Imperial Coll Sci Technol & Med, Div Cell & Mol Biol, London SW7 2AZ, England
[6] Miyazaki Univ, Frontier Sci Res Ctr, Miyazaki 8991692, Japan
基金
英国医学研究理事会; 英国惠康基金; 英国生物技术与生命科学研究理事会;
关键词
bacterial pathogenesis; bacterial protein secretion; bioinformatics; genomics; virulence;
D O I
10.1073/pnas.0604891103
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:14941 / 14946
页数:6
相关论文
共 50 条
[1]   Gapped BLAST and PSI-BLAST: a new generation of protein database search programs [J].
Altschul, SF ;
Madden, TL ;
Schaffer, AA ;
Zhang, JH ;
Zhang, Z ;
Miller, W ;
Lipman, DJ .
NUCLEIC ACIDS RESEARCH, 1997, 25 (17) :3389-3402
[2]   SopD2 is a novel type III secreted effector of Salmonella typhimurium that targets late endocytic compartments upon delivery into host cells [J].
Brumell, JH ;
Kujat-Choy, S ;
Brown, NF ;
Vallance, BA ;
Knodler, LA ;
Finlay, BB .
TRAFFIC, 2003, 4 (01) :36-48
[3]   The virulence plasmid pWR100 and the repertoire of proteins secreted by the type III secretion apparatus of Shigella flexneri [J].
Buchrieser, C ;
Glaser, P ;
Rusniok, C ;
Nedjari, H ;
d'Hauteville, H ;
Kunst, F ;
Sansonetti, P ;
Parsot, C .
MOLECULAR MICROBIOLOGY, 2000, 38 (04) :760-771
[4]   Structure of the Rho-activating domain of Escherichia coli cytotoxic necrotizing factor 1 [J].
Buetow, L ;
Flatau, G ;
Chiu, K ;
Boquet, P ;
Ghosh, P .
NATURE STRUCTURAL BIOLOGY, 2001, 8 (07) :584-588
[5]   Common infection strategies of plant and animal pathogenic bacteria [J].
Büttner, D ;
Bonas, U .
CURRENT OPINION IN PLANT BIOLOGY, 2003, 6 (04) :312-319
[6]   EspFU is a translocated EHEC effector that interacts with Tir and N-WASP and promotes nck-independent actin assembly [J].
Campellone, KG ;
Robbins, D ;
Leong, JM .
DEVELOPMENTAL CELL, 2004, 7 (02) :217-228
[7]   A high-throughput, near-saturating screen for type III effector genes from Pseudomonas syringae [J].
Chang, JH ;
Urbach, JM ;
Law, TF ;
Arnold, LW ;
Hu, A ;
Gombar, S ;
Grant, SR ;
Ausubel, FM ;
Dangl, JL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (07) :2549-2554
[8]   Identification of the secretion and translocation domain of the enteropathogenic and enterohemorrhagic Escherichia coli effector Cif, using TEM-1 β-lactamase as a new fluorescence-based reporter [J].
Charpentier, X ;
Oswald, E .
JOURNAL OF BACTERIOLOGY, 2004, 186 (16) :5486-5495
[9]   ColiBASE:: an online database for Escherichia coli, Shigella and Salmonella comparative genomics [J].
Chaudhuri, RR ;
Khan, AM ;
Pallen, MJ .
NUCLEIC ACIDS RESEARCH, 2004, 32 :D296-D299
[10]   Genomic mining type III secretion system effectors in Pseudomonas syringae yields new picks for all TTSS prospectors [J].
Collmer, A ;
Lindeberg, M ;
Petnicki-Ocwieja, T ;
Schneider, DJ ;
Alfano, JR .
TRENDS IN MICROBIOLOGY, 2002, 10 (10) :462-469