Zhang Weishan, Jiang Zheng, Mi Kaixia
CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Medical School, University of Chinese Academy of Sciences, Beijing 101408, China.
Cells. 2025 Jun 9;14(12):867. doi: 10.3390/cells14120867.
(Mtb) is a major global health threat, exacerbated by the emergence of antibiotic-resistant strains. This study investigated fluoroquinolone resistance protein A (MfpA), which enhances mycobacterial survival by targeting host mitochondria and regulating apoptosis. Wild-type (WT) and knockout (KO) (BCG) strains, a common model for Mtb, were utilized to examine host cell responses. Compared to WT strains, KO strains showed reduced colony-forming units (CFUs), elevated TNF-α and IL-6 levels, and increased apoptosis. MfpA was found to localize to mitochondria, increasing ROS production and disrupting mitochondrial membrane potential. Transcriptomic analysis revealed that MfpA modulated the NF-κB signaling pathway, regulating the expression of . These results suggest that MfpA drives both antibiotic resistance and virulence by suppressing apoptosis via the mitochondrial and NF-κB pathways, promoting mycobacterial persistence. Studies using BCG provide valuable insight into Mtb's survival mechanisms, highlighting MfpA's dual role in resistance and pathogenesis.
结核分枝杆菌（Mtb）是全球主要的健康威胁，抗生素耐药菌株的出现使其情况更加恶化。本研究调查了氟喹诺酮抗性蛋白A（MfpA），它通过靶向宿主线粒体和调节细胞凋亡来提高分枝杆菌的存活率。利用野生型（WT）和基因敲除（KO）卡介苗（BCG）菌株（一种常见的Mtb模型）来检测宿主细胞反应。与WT菌株相比，KO菌株的集落形成单位（CFU）减少，肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平升高，细胞凋亡增加。发现MfpA定位于线粒体，增加活性氧（ROS）的产生并破坏线粒体膜电位。转录组分析表明，MfpA调节核因子-κB（NF-κB）信号通路，调节……的表达。这些结果表明，MfpA通过线粒体和NF-κB途径抑制细胞凋亡，从而驱动抗生素耐药性和毒力，促进分枝杆菌的持续存在。使用卡介苗的研究为Mtb的生存机制提供了有价值的见解，突出了MfpA在耐药性和发病机制中的双重作用。
