Transient shielding of intimin and the type III secretion system of enterohemorrhagic and enteropathogenic Escherichia coli by a group 4 capsule
Transient shielding of intimin and the type III secretion system of enterohemorrhagic and enteropathogenic Escherichia coli by a group 4 capsule
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DOI：
10.1128/jb.00440-08
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发表时间：
2008-07-01
影响因子：
3.2
通讯作者：
Rosenshine, Ilan
中科院分区：
文献类型：
--
作者：
Shifrin, Yulia;Peleg, Adi;Rosenshine, Ilan
肠出血性和肠致病性大肠杆菌（EHEC和EPEC，分别）菌株代表了一个主要的全球性健康问题。它们的毒力由一系列毒力因子的协同活性介导，包括毒素、III型蛋白分泌系统（TTSS）、皮利等。我们以前发现EPEC O127形成了第4组胶囊（G4C），在这份报告中，我们发现EHEC O157也产生了G4C，其组装依赖于etp，etk和wzy基因。我们进一步表明，在感染后的早期时间点，这些G4C似乎掩盖了表面结构，包括内膜和TTSS。这种掩蔽作用抑制了EPEC和EHEC与组织培养的上皮细胞的附着，降低了它们诱导肌动蛋白形成的能力，并减弱了TTSS介导的蛋白质易位到宿主细胞中。重要的是，我们发现Ler，一个正性调节因子的intimin和TTSS基因，抑制胶囊相关基因的表达，包括etp和etk。因此，TTSS和G4C的表达被相反地调节，并且在TTSS表达时胶囊产生减少。事实上，在感染后较晚的时间点，缩小的包膜不再干扰内膜和TTSS的活性。值得注意的是，通过使用兔婴儿模型，我们发现EHEC G4C是兔大肠有效定植所必需的。两者合计，我们的研究结果表明，时间表达的胶囊，这是协调的TTSS，需要最佳的EHEC定植的宿主肠道。
Enterohemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC, respectively) strains represent a major global health problem. Their virulence is mediated by the concerted activity of an array of virulence factors including toxins, a type III protein secretion system (TTSS), pili, and others. We previously showed that EPEC O127 forms a group 4 capsule (G4C), and in this report we show that EHEC O157 also produces a G4C, whose assembly is dependent on the etp, etk, and wzy genes. We further show that at early time points postinfection, these G4Cs appear to mask surface structures including intimin and the TTSS. This masking inhibited the attachment of EPEC and EHEC to tissue-cultured epithelial cells, diminished their capacity to induce the formation of actin pedestals, and attenuated TTSS-mediated protein translocation into host cells. Importantly, we found that Ler, a positive regulator of intimin and TTSS genes, represses the expression of the capsule-related genes, including etp and etk. Thus, the expression of TTSS and G4C is conversely regulated and capsule production is diminished upon TTSS expression. Indeed, at later time points postinfection, the diminishing capsule no longer interferes with the activities of intimin and the TTSS. Notably, by using the rabbit infant model, we found that the EHEC G4C is required for efficient colonization of the rabbit large intestine. Taken together, our results suggest that temporal expression of the capsule, which is coordinated with that of the TTSS, is required for optimal EHEC colonization of the host intestine.