Intestinal barrier dysfunction by enteropathogenic Escherichia coli is mediated by two effector molecules and a bacterial surface protein
Intestinal barrier dysfunction by enteropathogenic Escherichia coli is mediated by two effector molecules and a bacterial surface protein
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DOI：
10.1111/j.1365-2958.2004.04308.x
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发表时间：
2004-11-01
影响因子：
3.6
通讯作者：
Kenny, B
中科院分区：
文献类型：
--
作者：
Dean, P;Kenny, B
人类肠道病原体，肠致病性大肠杆菌（EPEC），通过依赖于效应蛋白注射到宿主细胞中的机制引起肠道疾病。据报道，EPEC需要一种效应物EspF来破坏肠细胞的紧密连接完整性并增加分子的细胞旁运动，这可能有助于腹泻。在这里，我们表明，不是一个，而是三个EPEC编码的因素在这个过程中发挥重要作用。因此，Map（线粒体相关蛋白）效应物显示：（i）与EspF一样对于破坏肠屏障功能是必需的，（ii）能够独立于EspF发挥功能，（iii）改变紧密连接结构，以及（iv）在不存在线粒体靶向的情况下介导这些作用。此外，外膜蛋白Intimin被证明对EspF和Map破坏肠屏障功能至关重要。Intimin的这种功能完全独立于其与其已知受体Tir的相互作用，揭示了Intimin与替代受体相互作用的生理学相关要求。这项工作表明，EPEC使用多个多功能蛋白质引起肠道细胞中的特异性反应，并且EPEC可以从其细胞外位置控制其注射的效应分子的活性。
The human intestinal pathogen, enteropathogenic Escherichia coli (EPEC), causes diarrhoeal disease by a mechanism that is dependent on the injection of effector proteins into the host cell. One effector, EspF, is reported to be required for EPEC to disrupt tight junction integrity of intestinal cells and increase the paracellular movement of molecules, which is likely to contribute to diarrhoea. Here, we show that not one but three EPEC-encoded factors play important roles in this process. Thus, the Map (Mitochondria-associated protein) effector is shown to: (i) be as essential as EspF for disrupting intestinal barrier function, (ii) be able to function independently of EspF, (iii) alter tight junction structure and (iv) mediate these effects in the absence of mitochondrial targeting. Additionally, the outer membrane protein Intimin is shown to be crucial for EspF and Map to disrupt the intestinal barrier function. This function of Intimin is completely independent of its interaction with its known receptor Tir, revealing a physiologically relevant requirement for Intimin interaction with alternative receptor(s). This work demonstrates that EPEC uses multiple multifunctional proteins to elicit specific responses in intestinal cells and that EPEC can control the activity of its injected effector molecules from its extracellular location.