Cytolethal distending toxin (CDT) is a bacterial toxin that initiates a eukaryotic cell cycle block at the G2 stage prior to mitosis. CDT is produced by a number of bacterial pathogens including: Campylobacter species, Escherichia coli, Salmonella enterica serovar Typhi, Shigella dystenteriae, enterohepatic Helicobacter species, Actinobacillus actinomycetemcomitans (the cause of aggressive periodontitis), and Haemophilus ducreyi (the cause of chancroid). The functional toxin is composed of three proteins; CdtB potentiates a cascade leading to cell cycle block, and CdtA and CdtC function as dimeric subunits, which bind CdtB and delivers it to the mammalian cell interior. Once inside the cell, CdtB enters the nucleus and exhibits a DNase I-like activity that results in DNA double-strand breaks. The eukaryotic cell responds to the DNA double-strand breaks by initiating a regulatory cascade that results in cell cycle arrest, cellular distension, and cell death. Mutations in CdtABC that cause any of the three subunits to lose function prevent the bacterial cell from inducing cytotoxicity. The result of CDT activity can differ somewhat depending on the eukaryotic cell types affected. Epithelial cells, endothelial cells, and keratinocytes undergo G2 cell cycle arrest, cellular distension, and death; fibroblasts undergo G1 and G2 arrest, cellular distension, and death; and immune cells undergo G2 arrest followed by apoptosis. CDT contributes to pathogenesis by inhibiting both cellular and humoral immunity via apoptosis of immune response cells, and by generating necrosis of epithelial-type cells and fibroblasts involved in the repair of lesions produced by pathogens resulting in slow healing and production of disease symptoms. Thus, CDT may function as a virulence factor in pathogens that produce the toxin.

中文翻译：

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细胞致死性膨胀毒素对细菌发病机制的贡献。

细胞致死性扩张性毒素（CDT）是一种细菌毒素，在有丝分裂之前的G2阶段启动了真核细胞周期阻滞。CDT由许多细菌性病原体产生，包括：弯曲杆菌属，大肠杆菌，肠炎沙门氏菌血清型伤寒杆菌，痢疾志贺氏菌，肠肝菌性幽门螺杆菌，放线杆菌放线杆菌（侵袭性牙周炎的原因）和杜氏嗜血杆菌（chancroid的病因）。功能性毒素由三种蛋白质组成。CdtB增强了导致细胞周期阻滞的级联反应，而CdtA和CdtC充当二聚体亚基，与CdtB结合并将其递送至哺乳动物细胞内部。一旦进入细胞，CdtB进入细胞核并表现出类似DNase I的活性，从而导致DNA双链断裂。真核细胞通过启动调节级联反应来响应DNA双链断裂，从而导致细胞周期停滞，细胞膨胀和细胞死亡。CdtABC中导致三个亚基丧失功能的突变可防止细菌细胞诱导细胞毒性。CDT活性的结果可能会有所不同，具体取决于受影响的真核细胞类型。上皮细胞，内皮细胞和角质形成细胞经历G2细胞周期停滞，细胞扩张和死亡。成纤维细胞经历G1和G2停滞，细胞扩张和死亡；免疫细胞会被G2阻滞，然后凋亡。CDT通过免疫反应细胞的凋亡抑制细胞和体液免疫，从而促进发病机理，并且通过引起上皮型细胞和成纤维细胞的坏死而参与到由病原体产生的损伤的修复中，从而导致缓慢的愈合和疾病症状的产生。因此，CDT可能在产生毒素的病原体中充当毒力因子。