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脑内入侵是由 InlF 和宿主细胞中间丝蛋白介导的。

Invasion of the Brain by Is Mediated by InlF and Host Cell Vimentin.

机构信息

Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA

Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.

出版信息

mBio. 2018 Feb 27;9(1):e00160-18. doi: 10.1128/mBio.00160-18.

Abstract

is a facultative intracellular bacterial pathogen that is frequently associated with food-borne infection. Of particular concern is the ability of to breach the blood-brain barrier, leading to life-threatening meningitis and encephalitis. The mechanisms used by bacterial pathogens to infect the brain are not fully understood. Here we show that is able to utilize vimentin for invasion of host cells. Vimentin is a type III intermediate filament protein within the cytosol but is also expressed on the host cell surface. We found that interaction with surface-localized vimentin promoted bacterial uptake. Furthermore, in the absence of vimentin, colonization of the brain was severely compromised in mice. The virulence factor InlF was found to bind vimentin and was necessary for optimal bacterial colonization of the brain. These studies reveal a novel receptor-ligand interaction that enhances infection of the brain by and highlights the importance of surface vimentin in host-pathogen interactions. is an intracellular bacterial pathogen that is capable of invading numerous host cells during infection. can cross the blood-brain barrier, leading to life-threatening meningitis. Here we show that an surface protein, InlF, is necessary for optimal colonization of the brain in mice. Furthermore, in the absence of vimentin, a cytosolic intermediate filament protein that is also present on the surface of brain endothelial cells, colonization of the brain was significantly impaired. We further show that InlF binds vimentin to mediate invasion of host cells. This work identifies InlF as a bacterial surface protein with specific relevance for infection of the brain and underscores the significance of host cell surface vimentin interactions in microbial pathogenesis.

摘要

是一种兼性细胞内细菌病原体,常与食源性感染有关。特别值得关注的是,能够穿透血脑屏障,导致危及生命的脑膜炎和脑炎。细菌病原体感染大脑的机制尚未完全了解。在这里,我们表明 能够利用波形蛋白入侵宿主细胞。波形蛋白是细胞溶胶中的 III 型中间丝蛋白,但也表达在宿主细胞表面。我们发现,与表面定位的波形蛋白相互作用促进了细菌的摄取。此外,在没有波形蛋白的情况下,细菌在小鼠大脑中的定植严重受损。发现 毒力因子 InlF 与波形蛋白结合,是细菌在大脑中最佳定植所必需的。这些研究揭示了一种新的受体-配体相互作用,增强了细菌对大脑的感染,并强调了表面波形蛋白在宿主-病原体相互作用中的重要性。是一种能够在感染过程中入侵多种宿主细胞的细胞内细菌病原体。能够穿过血脑屏障,导致危及生命的脑膜炎。在这里,我们表明,一种 表面蛋白 InlF,是在小鼠中最佳定植大脑所必需的。此外,在没有波形蛋白的情况下,波形蛋白是一种存在于脑内皮细胞表面的细胞溶胶中间丝蛋白,大脑的定植显著受损。我们进一步表明,InlF 结合波形蛋白来介导宿主细胞的入侵。这项工作确定了 InlF 作为一种细菌表面蛋白,与大脑感染具有特定的相关性,并强调了宿主细胞表面波形蛋白相互作用在微生物发病机制中的重要性。

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