Citrobacter rodentium infection causes both mitochondrial dysfunction and intestinal epithelial barrier disruption in vivo:: role of mitochondrial associated protein (Map)
Citrobacter rodentium infection causes both mitochondrial dysfunction and intestinal epithelial barrier disruption in vivo:: role of mitochondrial associated protein (Map)
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DOI：
10.1111/j.1462-5822.2006.00741.x
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发表时间：
2006-10-01
影响因子：
3.4
通讯作者：
Vallance, Bruce A.
中科院分区：
文献类型：
--
作者：
Ma, Caixia;Wickham, Mark E.;Vallance, Bruce A.
肠致病性大肠杆菌（EPEC）和肠出血性大肠杆菌。大肠杆菌是一种非侵入性的附着/消失（A/E）细菌病原体，其感染宿主的肠上皮，引起严重的肠道疾病。这些细菌利用III型分泌装置将效应分子递送到宿主细胞中，破坏细胞功能。线粒体相关蛋白（Map）是一种靶向宿主细胞线粒体的多功能效应蛋白，在体外参与感染诱导的上皮屏障功能障碍。不幸的是，这些行动的相关性EPEC诱导的疾病的发病机制是不确定的。使用啮齿柠檬酸杆菌，小鼠适应的A/E细菌，我们发现，地图与宿主细胞线粒体共定位，并在体内感染导致感染的结肠细胞的线粒体形态的破坏，通过电子显微镜评估。线粒体酶琥珀酸脱氢酶的组织化学染色也显示了感染的肠上皮细胞线粒体呼吸功能的显著丧失;然而，在感染Delta map菌株的小鼠中，这两种病理均减弱。C.啮齿动物Map也涉及体外和体内上皮屏障功能的破坏。因此，这些研究推进了我们对A/E病原体如何破坏宿主细胞功能和引起疾病的理解，表明Map有助于C.啮齿动物。
Enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli are non-invasive attaching/effacing (A/E) bacterial pathogens that infect their host's intestinal epithelium, causing severe diarrhoeal disease. These bacteria utilize a type III secretion apparatus to deliver effector molecules into host cells, subverting cellular function. Mitochondrial associated protein (Map) is a multifunctional effector protein that targets host cell mitochondria and contributes to infection-induced epithelial barrier dysfunction in vitro. Unfortunately, the relevance of these actions to the pathogenesis of EPEC-induced disease is uncertain. Using Citrobacter rodentium, a mouse-adapted A/E bacterium, we found that Map colocalized with host cell mitochondria, and that in vivo infection led to a disruption of mitochondrial morphology in infected colonocytes as assessed by electron microscopy. Histochemical staining for the mitochondrial enzyme succinate dehydrogenase also revealed a significant loss of mitochondrial respiratory function in the infected intestinal epithelium; however, both pathologies were attenuated in mice infected with a Delta map strain. C. rodentium Map was also implicated in the disruption of epithelial barrier function both in vitro and in vivo. These studies thus advance our understanding of how A/E pathogens subvert host cell functions and cause disease, demonstrating that Map contributes to the functional disruption of the intestinal epithelium during enteric infection by C. rodentium.