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Wei group identified the first receptor for Clostridium difficile Toxin B

时间:2015/5/15   放大字体 放小字体 打印


As a spore-forming anaerobic bacillus, Clostridium difficile (C. difficile) is responsible for severe and fatal pseudomembranous colitis, and it is the leading cause of antibiotic-associated diarrhea worldwide. C. difficile is listed as the most urgent antibiotic resistance threat, according to a recent report by Center for Disease Control and Prevention (U.S. Department of Health and Human Services) because it is estimated that there are 250,000 cases of Clostridium difficile infections (CDIs) annually in the United States alone, leading to 14,000 deaths, which cost about $1 billion annually for US hospitals. In China, CDIs also pose significant threat to community especially in health care settings.

C. difficile exerts its pathogenicity mainly by secreting toxin B (TcdB). However, little is known about how this toxin enters host cells to elicit its pathogenicity effect. Through high-throughput screening and genome editing technique, Dr. Wensheng Wei group reported the first identification of the TcdB cellular receptor, chondroitin sulfate proteoglycan 4 (CSPG4). Through direct binding, CSPG4 mediates the endocytosis of TcdB, and consequently its cytopathic effects. The discovery of the first TcdB receptor reveals a previously unsuspected role for CSPG4 and provides a new therapeutic target for the treatment of CDIs. In addition, Wei and his colleagues demonstrated that there exists an alternative receptor besides CSPG4 for TcdB. For over three decades, researchers all over the world have been trying hard to search for TcdB receptor(s). The redundancy feature of the toxin endocytosis pathways may explain why it is so difficult for the receptor identification.

This work was published in Cell Research (2015, 25:157-168; published online 30 December 2014) as a cover article (Chondroitin Sulphate Proteoglycan 4 Functions as the Cellular Receptor for Clostridium difficile Toxin B). The first author is Ph.D. student Pengfei Yuan from Wei group. This work was supported by funds from the National Natural Science Foundation of China, the National Basic Research Program of China, and the Peking-Tsinghua Center for Life Sciences.