Identification and inhibition of hydrolases in Mycobacterium tuberculosis

 描述（由申请人提供）：世界上三分之一的人口感染结核分枝杆菌，结核病（TB）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，前线抗结核药物对潜伏结核病的疗效欠佳。因此，确定治疗潜伏性结核病的新药靶点是任何结核病根除战略的组成部分。丝氨酸水解酶代表了一个有前途但研究不足的潜在新靶点家族。本研究将（1）分析丝氨酸水解酶活性和（2）测试在活跃生长和非复制潜伏期期间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确定结核分枝杆菌在潜伏期存活的重要靶点，并提供可优化用于结核病临床使用的治疗线索。

 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.