Dependence of Mycobacterium bovis BCG on anaerobic nitrate reductase for persistence is tissue specific
Dependence of Mycobacterium bovis BCG on anaerobic nitrate reductase for persistence is tissue specific
复制标题
DOI：
10.1128/iai.70.1.286-291.2002
复制
发表时间：
2002-01-01
影响因子：
3.1
通讯作者：
Bange, FC
中科院分区：
文献类型：
--
作者：
Fritz, C;Maass, S;Bange, FC
牛分枝杆菌BCG是目前唯一可用的抗结核疫苗，从毒性M.体外连续传代后，疫苗株至少保留了其部分原始毒力，因为其在免疫活性宿主中持续存在，偶尔可能在免疫缺陷宿主中引起致命疾病。分枝杆菌在体内的持久性被认为取决于厌氧代谢，这是一个明显的矛盾，因为所有分枝杆菌都是专性需氧菌。在这里，我们报告说，M。缺乏厌氧硝酸盐还原酶（NarGHJI）（硝酸盐呼吸所必需的酶）的牛BCG未能在免疫活性（BALB/c）小鼠的肺、肝和肾中持续存在。然而，在免疫缺陷（SCID）小鼠中，尽管narG被破坏，但杆菌引起慢性感染，即使突变体在肺、肝和肾中的生长严重受损。BCG在任一小鼠品系脾脏中的持续性和生长似乎基本上不受厌氧硝酸还原酶缺乏的影响，表明该酶在发病机制中的作用是组织特异性的。这些数据首先表明，厌氧硝酸盐还原是必不可少的代谢M。牛卡介苗在免疫活性但非免疫缺陷小鼠中的作用，其次，它在分枝杆菌疾病中的作用是组织特异性的，这两个观察结果对分枝杆菌的发病机制和疫苗开发具有重要意义。
Mycobacterium bovis BCG, the only presently available vaccine against tuberculosis, was obtained from virulent M. bovis after serial passages in vitro. The vaccine strain retained at least some of its original virulence, as it persists in immune-competent hosts and occasionally may cause fatal disease in immune-deficient hosts. Mycobacterial persistence in vivo is thought to depend on anaerobic metabolism, an apparent paradox since all mycobacteria are obligate aerobes. Here we report that M. bovis BCG lacking anaerobic nitrate reductase (NarGHJI), an enzyme essential for nitrate respiration, failed to persist in the lungs, liver, and kidneys of immune-competent (BALB/c) mice. In immune-deficient (SCID) mice, however, bacilli caused chronic infection despite disruption of narG, even if growth of the mutant was severely impaired in lungs, liver, and kidneys. Persistence and growth of BCG in the spleens of either mouse strain appeared largely unaffected by lack of anaerobic nitrate reductase, indicating that the role of the enzyme in pathogenesis is tissue specific. These data suggest first that anaerobic nitrate reduction is essential for metabolism of M. bovis BCG in immune-competent but not immune-deficient mice and second that its role in mycobacterial disease is tissue specific, both of which are observations with important implications for pathogenesis of mycobacteria and vaccine development.