The recalcitrance of pathogenic Mycobacterium tuberculosis, the agent of tuberculosis, to eradication is due to various factors allowing bacteria to escape from stress situations. The mycobacterial chaperone GroEL1, overproduced after macrophage entry and under oxidative stress, could be one of these key players. We previously reported that GroEL1 is necessary for the biosynthesis of phthiocerol dimycocerosate, a virulence-associated lipid and for reducing antibiotic susceptibility. In the present study, we showed that GroEL1, bearing a unique C-terminal histidine-rich region, is required for copper tolerance during Mycobacterium bovis BCG biofilm growth. Mass spectrometry analysis demonstrated that GroEL1 displays high affinity for copper ions, especially at its C-terminal histidine-rich region. Furthermore, the binding of copper protects GroEL1 from destabilization and increases GroEL1 ATPase activity. Altogether, these findings suggest that GroEL1 could counteract copper toxicity, notably in the macrophage phagosome, and further emphasizes that M. tuberculosis GroEL1 could be an interesting antitubercular target.

中文翻译：

---

铜与结核分枝杆菌 GroEL1 之间的相互作用。

致病性结核分枝杆菌（结核病的病原体）难以根除是由于各种因素使细菌能够摆脱压力情况。分枝杆菌伴侣 GroEL1 在巨噬细胞进入和氧化应激后过度产生，可能是这些关键参与者之一。我们之前曾报道过，GroEL1 对苯二酚二霉菌酸酯（一种毒力相关脂质）的生物合成和降低抗生素敏感性是必需的。在本研究中，我们表明 GroEL1 具有独特的 C 端富含组氨酸的区域，是牛分枝杆菌期间铜耐受性所必需的BCG 生物膜生长。质谱分析表明，GroEL1 对铜离子具有高亲和力，尤其是在其 C 端富含组氨酸的区域。此外，铜的结合保护 GroEL1 免于不稳定并增加 GroEL1 ATPase 活性。总之，这些发现表明 GroEL1 可以抵消铜毒性，特别是在巨噬细胞吞噬体中，并进一步强调结核分枝杆菌GroEL1 可能是一个有趣的抗结核靶点。