文献类型：期刊文献

英文题名：GlnR-mediated regulation of KstR controls cholesterol catabolism in Mycobacterium smegmatis

作者：Ma, Heng[1];Liu, Wei-Bing[2];Zhang, Xiao-Peng[2];Hu, Hao-Qi[2];Gu, Sheng-Di[2];Yuan, Hao[2];Ye, Bang-Ce[1,2,3]

机构：[1]Shihezi Univ, Sch Chem & Chem Engn, Xinjiang 832000, Peoples R China;[2]East China Univ Sci & Technol, Lab Biosyst & Microanal, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[3]Zhejiang Univ Technol, Inst Engn Biol & Hlth, Collaborat Innovat Ctr Yangtze River Delta Reg Gr, Coll Pharmaceut Sci, Hangzhou, Zhejiang, Peoples R China

年份：2022

卷号：69

期号：3

起止页码：1209

外文期刊名：BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY

收录：;EI(收录号：20212210434423);WOS:【SCI-EXPANDED(收录号:WOS:000655117400001)】；

基金：This work was supported by grants from the National Natural Science Foundation of China (31730004), the General Program of Shanghai Natural Science Foundation (19ZR1413700), and Shanghai undergraduate training program for innovation and entrepreneurship (S19023).

语种：英文

外文关键词：cholesterol degradation; differential gene expression; environmental nitrogen; macrophage invasion; tuberculosis

摘要：Tuberculosis, caused by mycobacteria, continues to pose a substantial public health threat. Mycobacteria typically use cholesterol from the membranes of host macrophages as a carbon and energy source. Most genes that control cholesterol degradation are regulated by KstR, which is highly conserved in Mycobacterium tuberculosis and Mycobacterium smegmatis. Through bioinformatic analysis, we found a typical global nitrogen regulator (GlnR)-binding motif (CCGAC-AACAGT-GACAC) in the promoter region of kstR of M. smegmatis, and we determined its binding activity in vitro using electrophoretic mobility shift assays. Using RT-qPCR, we found that nine genes involved in side-chain or sterol-ring oxidation were upregulated in a Delta glnR M. smegmatis strain compared to the WT strain and glnR-complemented strains under nitrogen limitation. ATP assays in macrophages revealed that coordinated GlnR-KstR regulation significantly reduced the viability of M. smegmatis in macrophages. Thus, we found that various genes involved in cholesterol catabolism are regulated by GlnR via KstR in response to environmental nitrogen, and that they further affect the invasive ability of M. smegmatis. These findings revealed a novel regulatory mechanism of cholesterol catabolism, which may be useful in the development of new strategies for controlling tuberculosis.