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Clostridium difficile binary toxin CDT

机译:艰难梭菌二元毒素CDT

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摘要

Binary toxin (CDT) is frequently observed in Clostridium difficile strains associated with increased severity of C. difficile infection (CDI). CDT belongs to the family of binary ADP-ribosylating toxins consisting of two separate toxin components: CDTa, the enzymatic ADP-ribosyltransferase which modifies actin, and CDTb which binds to host cells and translocates CDTa into the cytosol. CDTb is activated by serine proteases and binds to lipolysis stimulated lipoprotein receptor. ADP-ribosylation induces depolymerization of the actin cytoskeleton. Toxin-induced actin depolymerization also produces microtubule-based membrane protrusions which form a network on epithelial cells and increase bacterial adherence. Multiple clinical studies indicate an association between binary toxin genes in C. difficile and increased 30-d CDI mortality independent of PCR ribotype. Further studies including measures of binary toxin in stool, analyses of CDI mortality caused by CDT-producing strains, and examination of the relationship of CDT expression to TcdA and TcdB toxin variants and PCR ribotypes are needed.
机译:与艰难梭菌感染(CDI)的严重程度增加相关的艰难梭菌菌株中经常观察到二进制毒素(CDT)。 CDT属于由两个单独的毒素成分组成的二元ADP-核糖基化毒素家族:CDTa(修饰肌动蛋白的酶促ADP-核糖基转移酶)和与宿主细胞结合并将CDTa转运到细胞质中的CDTb。 CDTb被丝氨酸蛋白酶激活,并与脂解刺激的脂蛋白受体结合。 ADP-核糖基化诱导肌动蛋白细胞骨架解聚。毒素诱导的肌动蛋白解聚也产生基于微管的膜突出物,其在上皮细胞上形成网络并增加细菌粘附。多项临床研究表明,艰难梭菌中的二进制毒素基因与30 d CDI死亡率升高之间的关联与PCR核型无关。还需要进一步的研究,包括测量粪便中的二进制毒素,分析由产生CDT的菌株引起的CDI死亡率以及检查CDT表达与TcdA和TcdB毒素变体以及PCR核型之间的关系。

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