Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
PLoS One. 2012;7(8):e43429. doi: 10.1371/journal.pone.0043429. Epub 2012 Aug 31.
Mycobacterium tuberculosis, the etiologic agent of tuberculosis (TB) possesses at least five genes predicted to encode proteins with NlpC/P60 hydrolase domains, including the relatively uncharacterized Rv2190c. As NlpC/P60 domain-containing proteins are associated with diverse roles in bacterial physiology, our objective was to characterize Rv2190c in M. tuberculosis growth and virulence. Our data indicate that lack of Rv2190c is associated with impaired growth, both in vitro and during an in vivo mouse model of TB. These growth defects are associated with altered colony morphology and phthiocerol dimycocerosate levels, indicating that Rv2190c is involved in cell wall maintenance and composition. In addition, we have demonstrated that Rv2190c is expressed during active growth phase and that its protein product is immunogenic during infection. Our findings have significant implications, both for better understanding the role of Rv2190c in M. tuberculosis biology and also for translational developments.
结核分枝杆菌是结核病(TB)的病原体,它至少拥有五个被预测编码具有 NlpC/P60 水解酶结构域的蛋白的基因,其中包括相对不为人知的 Rv2190c。由于 NlpC/P60 结构域蛋白与细菌生理中的多种功能有关,我们的目标是研究结核分枝杆菌中 Rv2190c 的生长和毒力特性。我们的数据表明,缺乏 Rv2190c 与体外和体内 TB 小鼠模型中的生长受损有关。这些生长缺陷与菌落形态和 phthiocerol dimycocerosate 水平的改变有关,表明 Rv2190c 参与了细胞壁的维持和组成。此外,我们已经证明 Rv2190c 在活跃的生长阶段表达,并且其蛋白产物在感染期间具有免疫原性。我们的发现具有重要意义,不仅可以更好地了解 Rv2190c 在结核分枝杆菌生物学中的作用,而且可以为转化发展提供依据。