Enterohemorrhagic Escherichia coli O157:H7 produces Tir, which is translocated to the host cell membrane but is not tyrosine phosphorylated
Enterohemorrhagic Escherichia coli O157:H7 produces Tir, which is translocated to the host cell membrane but is not tyrosine phosphorylated
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DOI：
10.1128/iai.67.5.2389-2398.1999
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发表时间：
1999-05-01
影响因子：
3.1
通讯作者：
Finlay, BB
中科院分区：
文献类型：
--
作者：
DeVinney, R;Stein, M;Finlay, BB
肠出血性大肠杆菌（EHEC）O 157：H7致病机制的一个基本特征是与宿主细胞的紧密粘附，从而形成粘附和消退（A/E）损伤。在一种相关的病原体中，肠致病性E.大肠杆菌（EPEC）中，这种活性依赖于内膜蛋白受体Tir的易位，Tir在宿主细胞膜内变得酪氨酸磷酸化。相反，在粘附的EHEC细菌下方不发生酪氨酸磷酸化蛋白的积累，导致关于EHEC是否使用基于Tir的机制来粘附和A/E损伤形成的问题。在这份报告中，我们证明，肠出血性大肠杆菌产生一个功能性的TIR插入到宿主细胞膜，在那里它作为一个内膜受体。然而，与EPEC不同，在EHEC中，Tir不是酪氨酸磷酸化的，但在细菌粘附于上皮细胞和基座形成中起关键作用。肠出血性大肠杆菌在Luria-Bertani培养基中不能合成Tir，但在M9培养基中能分泌Tir，这表明Tir的合成和分泌在这两种病原体中可能受到不同的调节。EHEC Tir和EPEC Tir都结合内膜蛋白并聚焦细胞骨架重排，表明酪氨酸磷酸化对于基座形成是不需要的。EHEC和EPEC intimins在功能上是可互换的，但EHEC Tir对EHEC intimin的亲和力比对EPEC intimin的亲和力大得多。这些发现突出了EHEC和EPEC毒力机制之间的一些差异和相似之处，这些差异和相似之处可用于进一步确定基座形成的分子基础。
Intimate attachment to the host cell leading to the formation of attaching and effacing (A/E) lesions is an essential feature of enterohemorrhagic Escherichia coli (EHEC) O157:H7 pathogenesis. In a related pathogen, enteropathogenic E. coli (EPEC), this activity is dependent upon translocation of the intimin receptor, Tir, which becomes tyrosine phosphorylated within the host cell membrane, In contrast, the accumulation of tyrosine-phosphorylated proteins beneath adherent EHEC bacteria does not occur, leading to questions about whether EHEC uses a Tir-based mechanism for adherence and A/E lesion formation. In this report, we demonstrate that EHEC produces a functional Tir that is inserted into host cell membranes, where it serves as an intimin receptor. However, unlike in EPEC, in EHEC Tir is not tyrosine phosphorylated yet plays a key role in both bacterial adherence to epithelial cells and pedestal formation. EHEC, but not EPEC, was unable to synthesize Tir in Luria-Bertani medium but was able to secrete Tir into M9 medium, suggesting that Tir synthesis and secretion may be regulated differently in these two pathogens. EHEC Tir and EPEC Tir both bind intimin and focus cytoskeletal rearrangements, indicating that tyrosine phosphorylation is not needed for pedestal formation. EHEC and EPEC intimins are functionally interchangeable, but EHEC Tir shows a much greater affinity for EHEC intimin than for EPEC intimin, These findings highlight some of the differences and similarities between EHEC and EPEC virulence mechanisms, which can be exploited to further define the molecular basis of pedestal formation.