The ability to tolerate multiple host derived stresses, resist eradication and persist within the infected individuals is central to the pathogenicity of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB). Mycobacterial survival is contingent upon sensing environmental perturbations and initiating a fitting response to counter them. Therefore, understanding of molecular mechanisms underlying stress tolerance and sensing in Mtb is critical for devising strategies for TB control. Our study aims to delineate the role of ClpB, a heat shock protein of Hsp100 family, in the general stress response and persistence mechanisms of Mtb. We demonstrate that Mtb requires ClpB to survive under stressful conditions. Additionally, we show that ClpB is necessary for the bacteria to persist in latency-like conditions such as prolonged hypoxia and nutrient-starvation. The disruption of ClpB results in aberrant cellular morphology, impaired biofilm formation and reduced infectivity of Mtb ex vivo. Our study also reports an alternative role of ClpB as a chaperokine which elicits inflammatory response in host. We conclude that ClpB is essential for Mtb to survive within macrophages, and plays a crucial part in the maintenance of dormant Mtb bacilli in latent state. The absence of ClpB in human genome makes it an attractive choice as drug target for TB.

耐受多种宿主衍生的压力，抵抗根除并在感染的个体中持续存在的能力，对于结核分枝杆菌（TB）的结核分枝杆菌（Mtb）的致病性至关重要。分枝杆菌的存活取决于感测环境扰动并发起合适的反应来抵抗它们。因此，了解抗药性和Mtb感测的分子机制对于设计结核病控制策略至关重要。我们的研究旨在描述Hsp100家族热休克蛋白ClpB在Mtb的一般应激反应和持久机制中的作用。我们证明了Mtb需要ClpB在压力条件下生存。此外，我们表明，ClpB对于细菌在潜伏期状的条件下（例如长时间缺氧和营养缺乏）的持续存在是必要的。ClpB的破坏导致异常的细胞形态，受损的生物膜形成和降低的Mtb离体感染性。我们的研究还报告了ClpB作为伴侣蛋白在宿主中引起炎症反应的替代作用。我们得出的结论是ClpB对于Mtb在巨噬细胞中生存至关重要，并且在潜在的Mtb休眠菌的维持中起着至关重要的作用。人类基因组中ClpB的缺失使其成为结核病靶标的诱人选择。