梭菌纲
艰难梭菌毒素A
程序性细胞死亡
细胞凋亡
生物
艰难梭菌毒素B
信号转导
蛋白激酶B
毒素
半胱氨酸蛋白酶
毒力因子
半胱氨酸蛋白酶8
微生物学
免疫学
毒力
抗生素
细胞生物学
艰难梭菌
基因
生物化学
作者
William Tornel,Ishrya Sharma,Hiba Osmani,Shannon Moonah
标识
DOI:10.1093/infdis/jiad481
摘要
There is an urgent need for new nonantibiotic-based treatment strategies for Clostridioides difficile infection. C. difficile toxin B (TcdB) is a virulent factor that is essential for causing disease. Here, we investigated whether a survival-signaling pathway could protect against TcdB. We found significant increase in caspase-3 apoptotic activity in intestinal epithelial cells of mice exposed to TcdB. Subsequently, activation of the MIF-CD74-Akt prosurvival signaling pathway blocked TcdB-induced caspase-3 activity and intestinal epithelial cell death. This brief report provides proof-of-concept that targeting prosurvival pathways may represent a unique antibiotic-independent strategy for protecting against C. difficile toxin-mediated cell death.
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