Mycobacterium tuberculosis (Mtb) has evolved sophisticated surveillance mechanisms to neutralize the ROS-induces toxicity which otherwise would degrade a variety of biological molecules including proteins, nucleic acids and lipids. In the present study, we find that Mtb lacking the Rv0495c gene (ΔRv0495c) is presented with a highly oxidized cytosolic environment. The superoxide-induced lipid peroxidation resulted in altered colony morphology and loss of membrane integrity in ΔRv0495c. As a consequence, ΔRv0495c demonstrated enhanced susceptibility when exposed to various host-induced stress conditions. Further, as expected, we observed a mutant-specific increase in the abundance of transcripts that encode proteins involved in antioxidant defence. Surprisingly, despite showing a growth defect phenotype in macrophages, the absence of the Rv0495c enhanced the pathogenicity and augmented the ability of the Mtb to grow inside the host. Additionally, our study revealed that Rv0495c-mediated immunomodulation by the pathogen helps create a favorable niche for long-term survival of Mtb inside the host. In summary, the current study underscores the fact that the truce in the war between the host and the pathogen favours long-term disease persistence in tuberculosis. We believe targeting Rv0495c could potentially be explored as a strategy to potentiate the current anti-TB regimen.

结核分枝杆菌(Mtb) 已经进化出复杂的监测机制来中和 ROS 引起的毒性，否则这些毒性会降解多种生物分子，包括蛋白质、核酸和脂质。在本研究中，我们发现缺乏Rv0495c基因（Δ Rv0495c ）的 Mtb 呈现出高度氧化的胞质环境。超氧化物诱导的脂质过氧化导致Δ Rv0495c中集落形态的改变和膜完整性的丧失。因此，当暴露于各种宿主诱导的应激条件时，ΔRv0495c表现出增强的敏感性。此外，正如预期的那样，我们观察到编码参与抗氧化防御的蛋白质的转录物丰度出现突变特异性增加。令人惊讶的是，尽管巨噬细胞显示出生长缺陷表型，但Rv0495c的缺失增强了致病性并增强了 Mtb 在宿主体内生长的能力。此外，我们的研究表明，病原体Rv0495c 介导的免疫调节有助于为 Mtb 在宿主体内长期生存创造有利的生态位。总之，当前的研究强调了这样一个事实：宿主与病原体之间的战争休战有利于结核病的长期​​持续存在。我们相信，针对 Rv0495c 的研究有可能被探索为一种增强当前抗结核治疗方案的策略。