Tauroursodeoxycholic acid prevents Burkholderia pseudomallei-induced endoplasmic reticulum stress and is protective during melioidosis in mice.
Tauroursodeoxycholic acid prevents Burkholderia pseudomallei-induced endoplasmic reticulum stress and is protective during melioidosis in mice.
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牛磺熊去氧胆酸可预防类鼻疽伯克霍尔德杆菌诱导的内质网应激，并在小鼠类鼻疽期间具有保护作用
DOI：
10.1186/s12866-021-02199-x
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发表时间：
2021-05-04
期刊：
影响因子：
4.2
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Yuan S;Fang Y;Tang M;Hu Z;Rao C;Chen J;Xia Y;Zhang M;Yan J;Tang B;He X;Xie J;Mao X;Li Q
假鼻疽伯克霍尔德氏菌是一种兼性胞内细菌，是类鼻疽病的病原体，在疫区可导致高达40%的败血症相关死亡。然而，目前还没有有效的疫苗可用，耐药性也是类鼻疽病治疗的一大难题。因此，寻找治疗类鼻疽病新的临床治疗策略迫在眉睫。我们证明了牛磺酸脱氧胆酸(TUDCA)，一种临床上可用的内质网(ER)应激抑制剂，在体内和体外都能促进假鼻疽清除。在本研究中，我们研究了TUDCA对类鼻疽病小鼠存活的影响，发现TUDCA治疗显著降低了假鼻疽杆菌的细胞内存活率。从机制上，我们发现假鼻疽杆菌可诱导RAW264.7巨噬细胞的凋亡，并激活ER应激的IRE1和PERK信号通路。在体外，TUDCA治疗可以减轻假单胞菌诱导的内质网应激，而TUDCA在体内具有保护作用。综上所述，我们的研究表明，假鼻疽杆菌感染导致内质网应激诱导的细胞凋亡，而TUDCA在体内和体外都通过抑制ER应激诱导的细胞凋亡来增强对假鼻疽的清除，表明TUDCA可以作为一种潜在的替代疗法用于类鼻疽病的治疗。网上版载有补充材料，可在10.1186/s12866-021-02199-x查阅。
Burkholderia 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. We 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. Taken 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. The online version contains supplementary material available at 10.1186/s12866-021-02199-x.
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影响因子：
6.7
作者：
Qin QM;Pei J;Ancona V;Shaw BD;Ficht TA;de Figueiredo P
通讯作者：
de Figueiredo P
DOI：
10.1016/j.jmii.2013.03.011
发表时间：
2014-10-01
影响因子：
7.4
作者：
Hseu, You-Cheng;Sung, Jia-Chuen;Chen, Ssu Ching
通讯作者：
Chen, Ssu Ching
Rab32 GTPase 作为 miR-30b/c 的直接靶标，通过调节吞噬体成熟来控制类鼻疽伯克霍尔德氏菌的细胞内存活
影响因子：
6.7
作者：
Hu, Zhi-qiang;Rao, Cheng-long;Mao, Xu-hu
通讯作者：
Mao, Xu-hu
影响因子：
4.8
作者：
Ding, Wen-Xing;Ni, Hong-Min;Yin, Xiao-Ming
通讯作者：
Yin, Xiao-Ming
影响因子：
5.1
作者：
Elia AE;Lalli S;Monsurrò MR;Sagnelli A;Taiello AC;Reggiori B;La Bella V;Tedeschi G;Albanese A
通讯作者：
Albanese A