title: The Role of Rho GTPases in Toxicity of Clostridium difficile Toxins.
abstract: Clostridium difficile (C. difficile) is the main cause of antibiotic-associated diarrhea prevailing in hospital settings. In the past decade, the morbidity and mortality of C. difficile infection (CDI) has increased significantly due to the emergence of hypervirulent strains. Toxin A (TcdA) and toxin B (TcdB), the two exotoxins of C. difficile, are the major virulence factors of CDI. The common mode of action of TcdA and TcdB is elicited by specific glucosylation of Rho-GTPase proteins in the host cytosol using UDP-glucose as a co-substrate, resulting in the inactivation of Rho proteins. Rho proteins are the key members in many biological processes and signaling pathways, inactivation of which leads to cytopathic and cytotoxic effects and immune responses of the host cells. It is supposed that Rho GTPases play an important role in the toxicity of C. difficile toxins. This review focuses on recent progresses in the understanding of functional consequences of Rho GTPases glucosylation induced by C. difficile toxins and the role of Rho GTPases in the toxicity of TcdA and TcdB.
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology (SCUT), Guangzhou 510006, China. shuyichan@foxmail.com.
authors.forename: Shuyi
authors.initials: S
authors.lastname: Chen
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology (SCUT), Guangzhou 510006, China. chunlis@163.com.
authors.forename: Chunli
authors.initials: C
authors.lastname: Sun
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology (SCUT), Guangzhou 510006, China. yingzi224926@163.com.
authors.forename: Haiying
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology (SCUT), Guangzhou 510006, China. jufangwang@scut.edu.cn.
authors.forename: Jufang
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000633:toxicity*; D001427:Bacterial Toxins / Q000737:chemistry / Q000633:toxicity*; D004768:Enterotoxins / Q000737:chemistry / Q000633:toxicity*; D006031:Glycosylation; D006801:Humans; D013329:Structure-Activity Relationship; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile; D020741:rho GTP-Binding Proteins
keywords: Clostridium difficile; Rho GTPase; toxin A (TcdA); toxin B (TcdB)