Division of Clinical Sciences, Infection and Immunity Research Centre, St. George's University of London, London, United Kingdom.
PLoS One. 2011;6(6):e20958. doi: 10.1371/journal.pone.0020958. Epub 2011 Jun 8.
Mycobacterium tuberculosis dosRS two-component regulatory system controls transcription of approximately 50 genes including hspX, acg and Rv2030c, in response to hypoxia and nitric oxide conditions and within macrophages and mice. The hspX lies between acg and Rv2030c. However, the functions of the dosR regulated genes in vitro and in vivo are largely unknown. Previously, we demonstrated that deletion of hspX gene produced a mutant which grew faster in macrophages and in mice. In this study, we attempted to determine the functions of acg and Rv2030c by gene inactivation. We demonstrate that Rv2030c is dispensable for virulence and growth. However, deletion of acg produced a mutant which is attenuated in both resting and activated macrophages and in acute and persistent murine infection models. Surprisingly, deletion of acg did not compromise the viability of the mutant to nitrosative and oxidative stresses in vitro and in vivo. In addition, when the WT and the acg mutants were treated with antibiotics such as the prodrugs nitrofurantoin and nitrofuran, the acg mutant became more sensitive than the WT strain to these drugs. This suggests that Acg may not function as a nitroreductase. These data indicate that acg encodes an essential virulence factor for M. tuberculosis and enables it to grow and survive in macrophages and in mouse organs.
结核分枝杆菌 dosRS 双组分调控系统控制约 50 个基因的转录，包括 hspX、acg 和 Rv2030c，以响应低氧和一氧化氮条件以及巨噬细胞和小鼠内的条件。hspX 位于 acg 和 Rv2030c 之间。然而，dosR 调节基因在体外和体内的功能在很大程度上是未知的。以前，我们证明 hspX 基因缺失会产生一种在巨噬细胞和小鼠中生长更快的突变体。在这项研究中，我们试图通过基因失活来确定 acg 和 Rv2030c 的功能。我们证明 Rv2030c 对于毒力和生长不是必需的。然而，acg 的缺失产生了一种在静止和激活的巨噬细胞以及急性和持续性小鼠感染模型中都减弱的突变体。令人惊讶的是，acg 的缺失并没有损害突变体在体外和体内对硝化和氧化应激的生存能力。此外，当 WT 和 acg 突变体用抗生素（如前药呋喃妥因和呋喃）处理时，acg 突变体对这些药物的敏感性比 WT 菌株更高。这表明 Acg 可能不作为硝基还原酶发挥作用。这些数据表明 acg 编码结核分枝杆菌的一个必需毒力因子，使其能够在巨噬细胞和小鼠器官中生长和存活。
