Lai Cheng-Kuo, Chen Yu-An, Lin Chun-Jung, Lin Hwai-Jeng, Kao Min-Chuan, Huang Mei-Zi, Lin Yu-Hsin, Chiang-Ni Chuan, Chen Chih-Jung, Lo U-Ging, Lin Li-Chiung, Lin Ho, Hsieh Jer-Tsong, Lai Chih-Ho
Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung UniversityTaoyuan, Taiwan; Department of Urology, University of Texas Southwestern Medical CenterDallas, TX, USA.
School of Medicine, Graduate Institute of Basic Medical Science, China Medical University Taichung, Taiwan.
Front Cell Infect Microbiol. 2016 Feb 9;6:9. doi: 10.3389/fcimb.2016.00009. eCollection 2016.
Cytolethal distending toxin (CDT), a genotoxin produced by Campylobacter jejuni, is composed of three subunits: CdtA, CdtB, and CdtC. CdtB is a DNase that causes DNA double-strand breaks (DSB) in the nucleus resulting in cell cycle arrest at the G2/M stage and apoptosis. CdtA and CdtC bind to cholesterol-rich microdomains on the cytoplasmic membrane, a process required for the delivery of CdtB to cells. Although a unique motif associated with cholesterol-binding activity has been identified in other pathogens, the mechanism underlying the interaction between the CdtA and CdtC subunits and membrane cholesterol remains unclear. Also, the processes of cell uptake and delivery of CdtB in host cells and the translocation of CdtB into the nucleus are only partially understood. In this review, we focus on the underlying relationship among CDT, membrane cholesterol, and the intracellular trafficking pathway as a unique mechanism for C. jejuni-induced pathogenesis. Moreover, we discuss the clinical aspects of a possible therapeutic application of CDT in cancer therapy. Understanding the molecular mechanism of CDT-host interactions may provide insights into novel strategies to control C. jejuni infection and the development of potential clinical applications of CDT.
细胞致死性膨胀毒素（CDT）是由空肠弯曲菌产生的一种基因毒素，由三个亚基组成：CdtA、CdtB和CdtC。CdtB是一种脱氧核糖核酸酶，可导致细胞核中的DNA双链断裂（DSB），从而使细胞周期停滞在G2/M期并引发细胞凋亡。CdtA和CdtC与细胞质膜上富含胆固醇的微结构域结合，这是将CdtB递送至细胞所必需的过程。尽管在其他病原体中已鉴定出与胆固醇结合活性相关的独特基序，但CdtA和CdtC亚基与膜胆固醇之间相互作用的潜在机制仍不清楚。此外，宿主细胞中CdtB的细胞摄取和递送过程以及CdtB向细胞核的转运仅得到部分了解。在本综述中，我们重点关注CDT、膜胆固醇和细胞内运输途径之间的潜在关系，这是空肠弯曲菌诱导发病机制的独特机制。此外，我们还讨论了CDT在癌症治疗中可能的治疗应用的临床方面。了解CDT与宿主相互作用的分子机制可能为控制空肠弯曲菌感染的新策略以及CDT潜在临床应用的开发提供见解。
