Mycobacterium tuberculosis Rv0790c inhibits the cellular autophagy at its early stage and facilitates mycobacterial survival.
Mycobacterium tuberculosis Rv0790c inhibits the cellular autophagy at its early stage and facilitates mycobacterial survival.
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结核分枝杆菌 Rv0790c 抑制早期细胞自噬并促进分枝杆菌存活
DOI：
10.3389/fcimb.2022.1014897
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发表时间：
2022
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
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作者：
Rv0790c 预计是由结核分枝杆菌 (Mtb) 编码的保守假设蛋白。然而，其在结核分枝杆菌感染中的作用仍然很大程度上未知。在这项研究中，我们发现 Rv0790c 在体外和体内均促进耻垢分枝杆菌 (Ms) 的细菌存活。外源表达 Rv0790c 的 Ms 的细菌负荷增加，而在 Rv0790c 敲除中，受感染巨噬细胞的细菌负荷减少。分析多个细胞过程以探索潜在机制。我们发现炎症调节和细胞凋亡诱导均不能促进 Rv0790c 介导的细菌存活。有趣的是，我们发现 Rv0790c 在早期阶段通过细胞自噬促进分枝杆菌的存活。自噬起始相关蛋白的免疫沉淀测定表明，Rv0790c 与 mTOR 相互作用并增强其活性，mTOR 下游底物 ULK-1（Ser757 处）和 P70S6K（Thr389 处）磷酸化水平增加证明了这一点。我们的研究发现了一种由分枝杆菌 Rv0790c 编码的新型自噬抑制因子，它抑制 Mtb 感染后细胞自噬诱导的早期阶段，并在维持细胞内分枝杆菌存活中发挥重要作用。它可能有助于了解结核分枝杆菌逃避宿主细胞降解的机制，并有可能开发预防和治疗结核病的新靶点。
Rv0790c is predicted to be a conserved hypothetical protein encoded by Mycobacterium tuberculosis (Mtb). However, its function in Mtb infection remains largely unknown. In this study, we found that Rv0790c promoted bacillary survival of M. smegmatis (Ms), both in vitro and in vivo. The bacillary burden of Ms exogenously expressing Rv0790c increased, whereas in Rv0790c-knockouts the bacillary burden decreased in infected macrophages. Multiple cellular processes were analyzed to explore the underlying mechanisms. We found that neither inflammatory regulation nor apoptotic induction were responsible for the promotion of bacillary survival mediated by Rv0790c. Interestingly, we found that Rv0790c facilitates mycobacterial survival through cellular autophagy at its early stage. Immunoprecipitation assay of autophagy initiation-related proteins indicated that Rv0790c interacted with mTOR and enhanced its activity, as evidenced by the increased phosphorylation level of mTOR downstream substrates, ULK-1, at Ser757 and P70S6K, at Thr389. Our study uncovers a novel autophagy suppressor encoded by mycobacterial Rv0790c, which inhibits the early stage of cellular autophagy induction upon Mtb infection and takes an important role in maintaining intracellular mycobacterial survival. It may aid in understanding the mechanism of Mtb evasion of host cellular degradation, as well as hold the potential to develop new targets for the prevention and treatment of tuberculosis.
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影响因子：
16
作者：
Linares, Juan F.;Duran, Angeles;Yajima, Tomoko;Pasparakis, Manolis;Moscat, Jorge;Diaz-Meco, Maria T.
通讯作者：
Diaz-Meco, Maria T.
影响因子：
21.3
作者：
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影响因子：
6.4
作者：
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通讯作者：
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影响因子：
2.8
作者：
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通讯作者：
Xu, Huimian
影响因子：
2.8
作者：
Denkin, S;Byrne, S;Zhang, Y
通讯作者：
Zhang, Y