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The Type III System-Secreted Effector EspZ Localizes to Host Mitochondria and Interacts with the Translocase of Inner Mitochondrial Membrane 17b

机译:III型系统分泌的效应子EspZ定位于宿主线粒体并与内部线粒体膜17b的转位酶相互作用。

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Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively) are attaching and effacing (A/E) bacterial pathogens that cause severe diarrheal disease worldwide. To cause disease, A/E pathogens require a type III secretion system, which facilitates transport of bacterial effector proteins directly into infected host cells. One of these effector proteins translocated by the type III secretion system, EspZ, is essential for A/E pathogen infection and functions to prevent rapid death of EPEC-infected cells. We further investigated the mechanism of EspZ-mediated protection of infected host cells and found that a severe decrease in host mitochondrial membrane potential (Δψm) occurs concurrently with host cell lysis during infection with EPEC lacking EspZ (ΔespZ). It was also demonstrated that EspZ localizes to host cell mitochondria and interacts with the translocase of inner mitochondrial membrane 17b (TIM17b). In addition, host cell cytotoxicity was exacerbated in the absence of TIM17b during wild-type (WT) EPEC infection. The findings of this study together provide the first evidence that EspZ localizes to host mitochondria and that TIM17b contributes to protection against rapid cell death during EPEC infection.
机译:肠致病性和肠出血性大肠杆菌(分别为EPEC和EHEC)正在附着并消灭(A / E)细菌病原体,这些病原体在全球范围内引起严重的腹泻病。为了引起疾病,A / E病原体需要III型分泌系统,该系统有助于将细菌效应蛋白直接转移到感染的宿主细胞中。通过III型分泌系统转运的这些效应蛋白之一,EspZ,对于A / E病原体感染至关重要,并具有防止EPEC感染细胞迅速死亡的功能。我们进一步研究了EspZ介导的感染宿主细胞保护的机制,发现宿主细胞线粒体膜电位(Δψ m )的严重降低与宿主细胞裂解同时感染缺少EspZ的EPEC(Δ espZ )。还证实EspZ定位于宿主细胞线粒体并与内部线粒体膜17b(TIM17b)的转位酶相互作用。此外,在野生型(WT)EPEC感染期间,在不存在TIM17b的情况下,宿主细胞的细胞毒性加剧。这项研究的发现共同为EspZ定位于宿主线粒体提供了第一个证据,而TIM17b有助于保护EPEC感染期间细胞快速死亡。

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