Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Key Laboratory of Aquatic Science of Chongqing, Institute of Modern Biopharmaceuticals, School of Life Sciences, Southwest University, Chongqing, 400715, China.
Chongqing Public Health Medical Center, Chongqing, China.
Commun Biol. 2024 Sep 19;7(1):1180. doi: 10.1038/s42003-024-06860-9.
The host limits Mycobacterium tuberculosis (Mtb) by enriching copper in high concentrations. This research investigates how Mtb escapes copper stress. The membrane protein encoded by Mtb Rv0102, when its homolog in M. smegmatis (MSMEG_4702) was knocked out, resulted in a fourfold decrease in intracellular copper levels and enhanced tolerance to elevated extracellular copper concentrations. Similarly, knockout mutants of its homolog in M. marinum (MMAR_0267) showed increased virulence in zebrafish and higher bacterial load within macrophages. In THP-1 cells infected with MMAR_0267 deletion mutants, the intracellular survival of these mutants increased, along with reduced THP-1 cell apoptosis. Deficiency in copper down-regulated the transcriptional level of the virulence factor CFP-10 in M. marinum, suppressed cytosolic signaling via the macrophage STING pathway, leading to decreased production of IFN-β and reduced cell apoptosis. In conclusion, these findings highlight the significant impact of copper on the survival and reproduction of mycobacteria, underscoring the importance of studying mycobacterial adaptation mechanisms in copper-rich environments.
宿主通过富集高浓度铜来限制结核分枝杆菌（Mtb）。本研究探讨了 Mtb 如何逃避铜胁迫。Mtb Rv0102 编码的膜蛋白，当其在耻垢分枝杆菌（MSMEG_4702）中的同源物被敲除时，细胞内铜水平降低了四倍，并增强了对高细胞外铜浓度的耐受性。同样，其在海分枝杆菌（MMAR_0267）中的同源物的敲除突变体在斑马鱼中表现出更高的毒力和巨噬细胞内更高的细菌负荷。在感染 MMAR_0267 缺失突变体的 THP-1 细胞中，这些突变体的细胞内存活增加，同时 THP-1 细胞凋亡减少。铜缺乏下调了海分枝杆菌毒力因子 CFP-10 的转录水平，抑制了巨噬细胞 STING 途径的胞质信号，导致 IFN-β 的产生减少和细胞凋亡减少。总之，这些发现强调了铜对分枝杆菌存活和繁殖的重要影响，突出了研究富含铜环境中分枝杆菌适应机制的重要性。
