Identification and inhibition of hydrolases in Mycobacterium tuberculosis

 描述(申请人提供)：世界上三分之一的人口感染结核分枝杆菌，这是结核病的病原体。这些人中的大多数都有无症状的潜伏感染，这是这种病原体的主要宿主。此外，一线抗结核药物对潜伏结核病的疗效也很差。因此，为潜伏性结核病确定新的药物靶点是根除结核病战略不可或缺的一部分。丝氨酸水解酶代表了一类有希望但未被充分研究的潜在新靶点。这项研究将(1)分析丝氨酸水解酶的活性，并(2)测试在活跃生长和非复制潜伏期抑制丝氨酸水解酶的治疗潜力。我们预计，这项研究的结果将有助于识别对分枝杆菌潜伏期生存至关重要的靶点，并提供可优化用于临床抗结核的治疗线索。

 DESCRIPTION (provided by applicant): One-third of the world's population is infected with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). The majority of these individuals have asymptomatic latent infections, which are the major reservoir for this pathogen. Also, frontline anti-TB drugs have only poor efficacy against latent TB. Therefore, identifying new drug targets for latent TB is integral to any strategy for TB eradication. The serine hydrolases represent a promising but understudied family of potential novel targets. This study will (1) profile serine hydrolase activity and (2) test the therapeutic potential of inhibiting serne hydrolases, both during active growth and non-replicating latency. We anticipate that the results of this study will aid the identification of targets important for mycobacterial survival during latency and provide therapeutic leads that can be optimized for clinical use against TB.