Serine/threonine-protein kinases in Mycobacterium tuberculosis (Mtb) form a preeminent regulatory system required to establish and maintain the infection in the host. Herein, we sought to decipher the biological role of PknL with the help of a gene replacement mutant RvΔpknL. Deletion of pknL results in the compromised growth under redox stress. The mutant showed significant survival defects in peritoneal macrophages, a significant decrease in the ability to establish infections and disseminate to the spleen in the murine model of infection. While the absence of pknL has no impact on either MIC or CFUs of ciprofloxacin and rifampicin treated bacilli, it increases the survival ~1.5–2.5 log fold upon isoniazid or ethambutol treatment. Collectively, data suggests that PknL aids in combating stress conditions in vitro, ex vivo, and in vivo and reduces the efficacy of isoniazid and ethambutol.

结核分枝杆菌( Mtb ) 中的丝氨酸/苏氨酸蛋白激酶形成了在宿主中建立和维持感染所需的卓越调节系统。在此，我们试图借助基因替换突变体RvΔpknL来破译 PknL 的生物学作用。pknL 的缺失导致在氧化还原胁迫下的生长受损。该突变体在腹腔巨噬细胞中显示出显着的存活缺陷，在小鼠感染模型中建立感染和传播到脾脏的能力显着降低。虽然没有pknL对环丙沙星和利福平处理的杆菌的 MIC 或 CFU 没有影响，它在异烟肼或乙胺丁醇处理后增加了约 1.5-2.5 log 倍的存活率。总的来说，数据表明 PknL 有助于在体外、离体和体内对抗压力条件，并降低异烟肼和乙胺丁醇的功效。