Kenny Brendan
Department of Pathology and Microbiology, School of Medical Sciences, University Walk, Bristol, UK.
Int J Med Microbiol. 2002 Feb;291(6-7):469-77. doi: 10.1078/1438-4221-00155.
Enteropathogenic E. coli (EPEC) is a prototypic member of the family of related 'attaching and effacing (A/E)' pathogens that induce diarrhoeal disease, especially to the young that can be fatal, of a wide range of mammalian species. Disease is correlated with the loss of absorptive gut epithelial microvilli and the reorganisation of host cytoskeletal proteins into pedestal-like structures beneath the adherent bacteria. These phenotypes are dependent on a pathogenicity island (LEE; Locus of Enterocyte Effacement) encoding a type III secretion system, secreted proteins, chaperone molecules, regulatory proteins and the bacterial outer membrane protein intimin. The type III secretion apparatus directs the transfer of specific proteins across the bacterial envelope, with a subset (EPEC secreted proteins - EspA, EspB and EspD) functioning to transfer effector proteins into host cells. These effector molecules subvert cellular processes that undoubtedly benefit the pathogen and contribute to disease. Three LEE-encoded EPEC effector molecules have so far been identified with one, Tir (Translocated intimin receptor), being transferred into host cells where it is modified by host kinases and becomes inserted into the plasma membrane to orchestrate cytoskeletal rearrangements linked to disease. This activity is dependent on its interaction with intimin and on tyrosine phosphorylation, with Tir-intimin interaction essential for virulence. A second effector Map, Mitochondrial-associated protein, is targeted to mitochondria where it has membrane-potential disrupting activity. The third, EspF disrupts intestinal barrier function and can induce host cell death by unknown mechanisms. Recent data relating to the mechanism by which Tir and Map function within host cells is discussed.
肠致病性大肠杆菌（EPEC）是相关“黏附与抹平（A/E）”病原体家族的典型成员，可引发腹泻疾病，尤其对多种哺乳动物幼崽而言可能是致命的。疾病与肠道吸收性上皮微绒毛的丧失以及宿主细胞骨架蛋白在黏附细菌下方重排形成基座样结构有关。这些表型依赖于一个致病岛（LEE；肠上皮细胞抹平位点），该致病岛编码III型分泌系统、分泌蛋白、伴侣分子、调节蛋白以及细菌外膜蛋白紧密素。III型分泌装置指导特定蛋白穿过细菌包膜，其中一部分（EPEC分泌蛋白——EspA、EspB和EspD）发挥作用将效应蛋白转运到宿主细胞中。这些效应分子破坏细胞过程，无疑对病原体有利并导致疾病。目前已鉴定出三种由LEE编码的EPEC效应分子，其中一种是Tir（易位紧密素受体），它被转运到宿主细胞中，在那里被宿主激酶修饰并插入质膜，以协调与疾病相关的细胞骨架重排。这种活性依赖于它与紧密素的相互作用以及酪氨酸磷酸化，Tir-紧密素相互作用对毒力至关重要。第二种效应分子Map，即线粒体相关蛋白，靶向线粒体，在那里具有破坏膜电位的活性。第三种效应分子EspF破坏肠道屏障功能，并可通过未知机制诱导宿主细胞死亡。本文讨论了与Tir和Map在宿主细胞内发挥作用机制相关的最新数据。
