World Journal of Microbiology and Biotechnology ( IF 4.0 ) Pub Date : 2021-08-11 , DOI: 10.1007/s11274-021-03117-z Swadha Kailoo 1 , Shreya 1 , Yatender Kumar 1
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Cytolethal Distending Toxin (CDT) belongs to the AB toxin family and is produced by a plethora of Gram-negative bacteria. Eight human-affecting enteropathogens harbor CDT that causes irritable bowel syndrome (IBS), dysentery, chancroid, and periodontitis worldwide. They have a novel molecular mode of action as they interfere in the eukaryotic cell-cycle progression leading to G2/M arrest and apoptosis. CDT, the first bacterial genotoxin described, is encoded in a single operon possessing three proteins, CdtA, CdtB, and CdtC. CdtA and CdtC are needed for the binding of the CDT toxin complex to the cholesterol-rich lipid domains of the host cell while the CdtB is the active moiety. Sequence and 3D structural-based analysis of CdtB showed similarities with nucleases and phosphatases, it was hypothesized that CdtB exercises a biochemical function identical to both these enzymes. CDT is secreted through the outer membrane vesicles from the producing bacteria. It is internalized in the target cells via clathrin-dependent endocytosis and translocated to the host cell nucleus through the Golgi complex and ER. This study discusses the virulence role of CDT, causing pathogenicity by acting as a tri-perditious complex in the CDT-producing species with an emphasis on its potential role as a biomarker and an anti-tumor agent.
Graphic abstract
中文翻译：
细胞致死膨胀毒素：从基因毒素到潜在的生物标志物和抗肿瘤靶点
细胞致死性膨胀毒素 (CDT) 属于 AB 毒素家族，由大量革兰氏阴性菌产生。八种影响人类的肠道病原体携带 CDT，可在全球范围内引起肠易激综合征 (IBS)、痢疾、软下疳和牙周炎。它们具有新的分子作用模式，因为它们会干扰导致 G 2的真核细胞周期进程/M 阻滞和细胞凋亡。CDT 是描述的第一种细菌基因毒素，它由一个操纵子编码，该操纵子具有三种蛋白质：CdtA、CdtB 和 CdtC。CDT 毒素复合物与宿主细胞富含胆固醇的脂质结构域结合需要 CdtA 和 CdtC，而 CdtB 是活性部分。CdtB 的序列和基于 3D 结构的分析显示出与核酸酶和磷酸酶的相似性，假设 CdtB 行使与这两种酶相同的生化功能。CDT 通过外膜囊泡从生产细菌中分泌出来。它通过网格蛋白依赖性内吞作用在靶细胞中内化，并通过高尔基复合体和内质网转移到宿主细胞核。本研究讨论了 CDT 的毒力作用，
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