Pro-Survival Pathway Protects from C. difficile Toxin-Mediated Cell Death.
Pro-Survival Pathway Protects from C. difficile Toxin-Mediated Cell Death.
复制标题
促生存途径可防止艰难梭菌毒素介导的细胞死亡。
DOI：
10.1093/infdis/jiad481
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Moonah,Shannon
中科院分区：
文献类型：
--
作者：
Tornel,William;Sharma,Ishrya;Osmani,Hiba;Moonah,Shannon
艰难梭菌感染迫切需要新的非抗生素治疗策略。艰难梭菌毒素B(TcdB)是一种致病必需的毒力因子。在这里，我们调查了生存信号通路是否可以保护TcdB。我们发现，暴露于TcdB的小鼠肠上皮细胞中caspase-3的凋亡活性显著增加。随后，MIF-CD74-Akt生存信号通路的激活阻断了TcdB诱导的caspase-3活性和肠上皮细胞死亡。这份简短的报告提供了概念证明，以生存途径为靶点可能代表了一种独特的抗生素非依赖性策略来预防C。艰难梭菌毒素介导的细胞死亡。
There is an urgent need for new nonantibiotic-based treatment strategies forClostridioides difficileinfection.C. difficiletoxin 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 againstC. difficiletoxin-mediated cell death.