An extensive repertoire of type III secretion effectors in Escherichia coli O157 and the role of lambdoid phages in their dissemination
An extensive repertoire of type III secretion effectors in Escherichia coli O157 and the role of lambdoid phages in their dissemination
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DOI：
10.1073/pnas.0604891103
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发表时间：
2006-10-03
影响因子：
11.1
通讯作者：
Pallen, Mark J.
中科院分区：
文献类型：
--
作者：
Tobe, Toru;Beatson, Scott A.;Pallen, Mark J.
大肠杆菌的几种致病菌株利用III型分泌物将“效应蛋白”注入人体细胞，然后颠覆真核细胞生物学，使细菌受益。我们已经利用生物信息学和实验方法来建立，在酒井株肠出血性大肠杆菌的效应库。大肠杆菌（EHEC）O 157：H7比以前认为的要大得多。同源性搜索导致鉴定出> 60个推定的效应基因。其中13个被认为是可能的假基因，而49个被认为是潜在的功能。总共有39种蛋白质被实验证实为效应物：31种通过蛋白质组学，28种通过易位测定。在蛋白质水平上，EHEC效应子序列属于> 20个家族。最大的家族，NleG家族，仅在Sakai株中就包含14个成员。肠出血性大肠杆菌还含有来自植物病原体（HopPtoH、HopW、AvrA）和志贺氏菌（OspD、OspE、OspG）的效应子的功能同源物，以及Map/IpgB家族的另外两个成员。编码已证实或预测的效应子的基因存在于分散在整个染色体中的> 20个可交换的效应子基因座中。重要的是，大多数功能性效应基因是由九个可交换的效应基因座编码的，这些基因座位于类胡萝卜原噬菌体内。因此，E.大肠杆菌与一个巨大的噬菌体“宏基因组”相连，充当致病性进化的坩埚。
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.