文献类型：期刊文献

英文题名：Regulatory mechanism of cholesterol transport via LtmA in Mycobacterium smegmatis

作者：Feng, Yu-Wei[1];Yin, Bin-Cheng[1];Li, Han-Bing[2];Liu, Wei-Bing[1];Ye, Bang-Ce[1]

机构：[1]East China Univ Sci & Technol, Lab Biosyst & Microanal, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Zhejiang Univ Technol, Coll Pharmaceut Sci, Hangzhou 310014, Zhejiang, Peoples R China

年份：2026

卷号：16

期号：1

外文期刊名：SCIENTIFIC REPORTS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001756674200002)】；

基金：This work was supported by National Key Research and Development Program of China (2021YFC2101000), and 2024 Double World-class Project.

语种：英文

外文关键词：LtmA; mce4; Cholesterol; Mycobacterium smegmatis

摘要：Mycobacterium tuberculosis, the causative agent of tuberculosis, is responsible for over a million deaths annually. This pathogen survives within macrophage phagosomes, exploiting cholesterol as a primary carbon and nutrient source. Cholesterol is a crucial metabolite for M. tuberculosis, contributing to energy production, cell wall integrity, immune modulation, and drug resistance. The Mammalian Cell Entry (MCE) protein family, in which the mce4 operon is particularly pivotal, facilitates cholesterol transport. This study investigates the regulatory effects of the transcription factor LtmA on the mce4 operon in Mycobacterium smegmatis, a model organism closely related to M. tuberculosis. LtmA, which possesses a unique TetR-type HTH domain, targets genes associated with lipid transport and metabolism. Using bioinformatics and Electrophoretic Mobility Shift Assay (EMSA), we identified and validated LtmA binding sequences within the mce4 regulatory region. Functional studies using ltmA knockdown and overexpression mutants revealed that LtmA acts as a repressor of the mce4 operon, thereby reducing cholesterol transport and impairing the intracellular survival of M. smegmatis within macrophages under cholesterol-dependent growth conditions. This work advances our knowledge of M. tuberculosis survival strategies, contributing significantly to global tuberculosis control efforts.