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Glucosyltransferase Activity of Clostridium difficile Toxin B Triggers Autophagy-mediated Cell Growth Arrest
He, Ruina ; Peng, Jingyu ; Yuan, Pengfei ; Yang, Junjiao ; Wu, Xiaoji ; Wang, Yinan ; Wei, Wensheng
刊名SCIENTIFIC REPORTS
2017
关键词PORE-FORMING TOXIN PHOSPHATIDYLINOSITOL 3-KINASE RHO-PROTEINS PSEUDOMEMBRANOUS COLITIS REGULATES AUTOPHAGY VIBRIO-CHOLERAE CULTURED-CELLS ANTHRAX TOXIN LETHAL TOXIN HOST-CELLS
DOI10.1038/s41598-017-11336-4
英文摘要Autophagy is a bulk cell-degradation process that occurs through the lysosomal machinery, and many reports have shown that it participates in microbial pathogenicity. However, the role of autophagy in Clostridium difficile infection (CDI), the leading cause of antibiotics-associated diarrhea, pseudomembranous colitis and even death in severe cases, is not clear. Here we report that the major virulent factor toxin B (TcdB) of Clostridium difficile elicits a strong autophagy response in host cells through its glucosyltransferase activity. Using a variety of autophagy-deficient cell lines, i.e. HeLa/ATG7(-/-), MEF/atg7(-/-), MEF/tsc2(-/-), we demonstrate that toxin-triggered autophagy inhibits host cell proliferation, which contributes to TcdB-caused cytopathic biological effects. We further show that both the PI3K complex and mTOR pathway play important roles in this autophagy induction process and consequent cytopathic event. Although the glucosyltransferase activity of TcdB is responsible for inducing both cell rounding and autophagy, there is no evidence suggesting the causal relationship between these two events. Taken together, our data demonstrate for the first time that the glucosyltransferase enzymatic activity of a pathogenic bacteria is responsible for host autophagy induction and the following cell growth arrest, providing a new paradigm for the role of autophagy in host defense mechanisms upon pathogenic infection.; National Science Foundation of China [NSFC31170126, NSFC81471909, NSFC31430025]; Beijing Advanced Innovation Center for Genomics at Peking University; Peking-Tsinghua Center for Life Sciences; SCI(E); ARTICLE; 7
语种英语
内容类型期刊论文
源URL[http://ir.pku.edu.cn/handle/20.500.11897/470942]  
专题生命科学学院
推荐引用方式
GB/T 7714
He, Ruina,Peng, Jingyu,Yuan, Pengfei,et al. Glucosyltransferase Activity of Clostridium difficile Toxin B Triggers Autophagy-mediated Cell Growth Arrest[J]. SCIENTIFIC REPORTS,2017.
APA He, Ruina.,Peng, Jingyu.,Yuan, Pengfei.,Yang, Junjiao.,Wu, Xiaoji.,...&Wei, Wensheng.(2017).Glucosyltransferase Activity of Clostridium difficile Toxin B Triggers Autophagy-mediated Cell Growth Arrest.SCIENTIFIC REPORTS.
MLA He, Ruina,et al."Glucosyltransferase Activity of Clostridium difficile Toxin B Triggers Autophagy-mediated Cell Growth Arrest".SCIENTIFIC REPORTS (2017).
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