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Clostridium difficile Toxin Biology
Annual Review of Microbiology ( IF 10.5 ) Pub Date : 2017-09-08 00:00:00 , DOI: 10.1146/annurev-micro-090816-093458
Klaus Aktories 1 , Carsten Schwan 1 , Thomas Jank 1
Affiliation  

Clostridium difficile is the cause of antibiotics-associated diarrhea and pseudomembranous colitis. The pathogen produces three protein toxins: C. difficile toxins A (TcdA) and B (TcdB), and C. difficile transferase toxin (CDT). The single-chain toxins TcdA and TcdB are the main virulence factors. They bind to cell membrane receptors and are internalized. The N-terminal glucosyltransferase and autoprotease domains of the toxins translocate from low-pH endosomes into the cytosol. After activation by inositol hexakisphosphate (InsP6), the autoprotease cleaves and releases the glucosyltransferase domain into the cytosol, where GTP-binding proteins of the Rho/Ras family are mono-O-glucosylated and, thereby, inactivated. Inactivation of Rho proteins disturbs the organization of the cytoskeleton and affects multiple Rho-dependent cellular processes, including loss of epithelial barrier functions, induction of apoptosis, and inflammation. CDT, the third C. difficile toxin, is a binary actin-ADP-ribosylating toxin that causes depolymerization of actin, thereby inducing formation of the microtubule-based protrusions. Recent progress in understanding of the toxins’ actions include insights into the toxin structures, their interaction with host cells, and functional consequences of their actions.

中文翻译:


艰难梭菌毒素生物学

艰难梭菌是与抗生素有关的腹泻和假膜性结肠炎的病因。该病原体产生三种蛋白质毒素:艰难梭菌毒素A(TcdA)和B(TcdB),以及艰难梭菌转移酶毒素(CDT)。单链毒素TcdA和TcdB是主要的毒力因子。它们与细胞膜受体结合并被内在化。毒素的N末端葡糖基转移酶和自体蛋白酶结构域从低pH内体转移到胞质溶胶中。在被六磷酸肌醇(InsP6)激活后,自蛋白酶裂解并释放出葡糖基转移酶结构域到胞质溶胶中,其中Rho / Ras家族的GTP结合蛋白是单-O-葡糖基化,从而失活。Rho蛋白的失活会干扰细胞骨架的组织,并影响多个Rho依赖性细胞过程,包括上皮屏障功能的丧失,凋亡的诱导和炎症。CDT是第三种艰难梭菌毒素,是一种二元肌动蛋白-ADP-核糖基化毒素,可导致肌动蛋白解聚,从而诱导形成基于微管的突起。在了解毒素作用方面的最新进展包括对毒素结构的了解,它们与宿主细胞的相互作用以及其作用的功能后果。

更新日期:2017-09-08
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