Tauroursodeoxycholic acid prevents Burkholderia pseudomallei-induced endoplasmic reticulum stress and is protective during melioidosis in mice

BMC Microbiology

Bin Tang¹  Xiaoyi He¹  Zhiqiang Hu¹  Chenglong Rao¹  Xuhu Mao¹  Yupei Xia¹  Qian Li¹  Jingmin Yan¹  Meijuan Zhang¹  Jiangao Chen²  Mengling Tang³  Siqi Yuan³  Yao Fang⁴  Jianping Xie⁵ 

[1] Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), 400038, Chongqing, China;Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), 400038, Chongqing, China;Department of General Medicine, Southwest Hospital, Army Medical University (Third Military Medical University), 400038, Chongqing, China;Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), 400038, Chongqing, China;Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, 400715, Chongqing, China;Department of Respiratory, General Hospital of Center Theater Command, 400070, Wuhan, China;Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, 400715, Chongqing, China;

关键词: Burkholderia pseudomallei;    Tauroursodeoxycholic acid;    Endoplasmic reticulum stress;    Apoptosis;    Survival;   

DOI  :  10.1186/s12866-021-02199-x

来源: Springer

【 摘 要 】

BackgroundBurkholderia pseudomallei, a facultative intracellular bacterium, is the aetiological agent of melioidosis that is responsible for up to 40% sepsis-related mortality in epidemic areas. However, no effective vaccine is available currently, and the drug resistance is also a major problem in the treatment of melioidosis. Therefore, finding new clinical treatment strategies in melioidosis is extremely urgent.ResultsWe demonstrated that tauroursodeoxycholic acid (TUDCA), a clinically available endoplasmic reticulum (ER) stress inhibitor, can promote B. pseudomallei clearance both in vivo and in vitro. In this study, we investigated the effects of TUDCA on the survival of melioidosis mice, and found that treatment with TUDCA significantly decreased intracellular survival of B. pseudomallei. Mechanistically, we found that B. pseudomallei induced apoptosis and activated IRE1 and PERK signaling ways of ER stress in RAW264.7 macrophages. TUDCA treatment could reduce B. pseudomallei-induced ER stress in vitro, and TUDCA is protective in vivo.ConclusionTaken together, our study has demonstrated that B. pseudomallei infection results in ER stress-induced apoptosis, and TUDCA enhances the clearance of B. pseudomallei by inhibiting ER stress-induced apoptosis both in vivo and in vitro, suggesting that TUDCA could be used as a potentially alternative treatment for melioidosis.

【 授权许可】

CC BY