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肠致病性大肠杆菌和鼠伤寒沙门氏菌感染过程中 CD147 的分布。

Distribution of CD147 During Enteropathogenic Escherichia coli and Salmonella enterica Serovar Typhimurium Infections.

机构信息

Department of Biological Sciences, Centre for Cell Biology, Development, and Disease, Simon Fraser University, Burnaby, British Columbia, Canada.

出版信息

Anat Rec (Hoboken). 2019 Dec;302(12):2224-2232. doi: 10.1002/ar.24235. Epub 2019 Sep 4.

Abstract

Enteropathogenic Escherichia coli (EPEC) and Salmonella enterica serovar Typhimurium (S. Typhimurium) are highly infectious gastrointestinal human pathogens. These microbes inject bacterial-derived effector proteins directly into the host cell cytosol as part of their disease processes. A common host subcellular target of these pathogens is the actin cytoskeleton, which is commandeered by the bacteria and is used during their attachment onto (EPEC) or invasion into (S. Typhimurium) the host cells. We previously demonstrated that the host enzyme cyclophilin A (CypA) is recruited to the actin-rich regions of EPEC pedestals and S. Typhimurium membrane ruffles. To further expand the growing catalogue of host proteins usurped by actin-hijacking bacteria, we examined the host plasma membrane protein and cognate receptor of CypA, CD147, during EPEC and S. Typhimurium infections. Here, we show that CD147 is enriched at the basolateral regions of pedestals but, unlike CypA, it is absent from their actin-rich core. We show that the CD147 recruitment to these areas requires EPEC pedestal formation and not solely bacteria-host cell contact. Additionally, we demonstrate that the depletion of CD147 by siRNA does not alter the formation of pedestals. Finally, we show that CD147 is also a component of actin-rich membrane ruffles generated during S. Typhimurium invasion of host cells. Collectively, our findings establish CD147 as another host component present at dynamic actin-rich structures formed during bacterial infections. Anat Rec, 302:2224-2232, 2019. © 2019 American Association for Anatomy.

摘要

肠致病性大肠杆菌(EPEC)和鼠伤寒沙门氏菌血清型 Typhimurium(S. Typhimurium)是高度传染性的胃肠道人类病原体。这些微生物作为其疾病过程的一部分,将细菌衍生的效应蛋白直接注射到宿主细胞质中。这些病原体的常见宿主亚细胞靶标是肌动蛋白细胞骨架,该骨架被细菌利用,用于其附着(EPEC)或入侵(S. Typhimurium)宿主细胞。我们之前证明,宿主酶亲环素 A(CypA)被招募到 EPEC 菌毛和 S. Typhimurium 膜皱襞的富含肌动蛋白的区域。为了进一步扩展被肌动蛋白劫持细菌篡夺的宿主蛋白不断增长的目录,我们在 EPEC 和 S. Typhimurium 感染期间检查了 CypA 的宿主质膜蛋白和同源受体 CD147。在这里,我们表明 CD147 在菌毛的基底外侧区域丰富,但与 CypA 不同,它不存在于富含肌动蛋白的核心中。我们表明,CD147 在这些区域的募集需要 EPEC 菌毛的形成,而不仅仅是细菌与宿主细胞的接触。此外,我们证明通过 siRNA 耗尽 CD147 不会改变菌毛的形成。最后,我们表明 CD147 也是宿主细胞感染期间 S. Typhimurium 入侵产生的富含肌动蛋白的膜皱襞的组成部分。总之,我们的研究结果确立 CD147 是另一种存在于细菌感染过程中形成的富含肌动蛋白的动态结构中的宿主成分。解剖学年鉴,302:2224-2232, 2019。© 2019 美国解剖学会。

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