Loyola University Chicago Stritch School of Medicine; Hines Veterans Affairs Hospital; Hines, IL USA.
Institute of Public Health Maribor; University of Maribor, Medical Faculty, and Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins; Ljubljana, Slovenia.
Gut Microbes. 2014 Jan-Feb;5(1):15-27. doi: 10.4161/gmic.26854. Epub 2013 Oct 31.
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.
二元毒素 (CDT) 在与艰难梭菌感染 (CDI) 严重程度增加相关的艰难梭菌菌株中经常被观察到。CDT 属于双功能 ADP-核糖基转移酶毒素家族，由两个单独的毒素成分组成：CDTa，即修饰肌动蛋白的酶 ADP-核糖基转移酶，以及与宿主细胞结合并将 CDTa 易位到细胞质中的 CDTb。CDTb 被丝氨酸蛋白酶激活，并与脂肪酶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还会产生基于微管的膜突起，在肠上皮细胞上形成网络，增加细菌黏附。多项临床研究表明，艰难梭菌中的二元毒素基因与增加的 30 天 CDI 死亡率之间存在关联，与 PCR 核糖体类型无关。需要进一步的研究，包括粪便中二元毒素的测量、由产 CDT 菌株引起的 CDI 死亡率分析，以及检查 CDT 表达与 TcdA 和 TcdB 毒素变体和 PCR 核糖体类型的关系。
