METABOLIC STRATEGIES OF LATENT MYCOBACTERIUM TUBERCULOSIS

无症状的分枝杆菌感染 以极少数细菌的存在为特征的，这些细菌很难 发现，可能不耐酸，也可能不能培养。这些 细菌已被提议在密闭的呼吸道内持续存在 哺乳动物的肺被描述为微嗜氧性 或厌氧条件。我们已经开始描述 伴随着适应的生化变化 微需氧生存和复制。我们已经证明了 分枝杆菌α-晶状体蛋白在 固定相和低氧条件下的毒力 分枝杆菌菌株。该蛋白得到了高效表达和纯化。 并被证明具有不依赖于ATP的伴侣功能和 防止老化细菌自溶。靶向基因 替换被用来创建阿尔法基因的基因敲除 结晶素蛋白在结核分枝杆菌强毒株中的表达 增长和复制能力大幅下降 感染的巨噬细胞模型。

Asymptomatic mycobacterial infections are characterized by the presence of very few bacilli which are difficult to find, may not be acid-fast, and may not be culturable. These bacilli have been proposed to persist within closed airways of the mammalian lung under what have been described as microaerophilic or anaerobic conditions. We have begun characterizing the biochemical changes which accompany the adaptation to microaerophilic survival and replication. We have shown that the mycobacterial a-crystallin protein is specifically expressed during stationary-phase and under low-oxygen conditions in virulent mycobacterial strains. This protein was overexpressed and purified and shown to have ATP-independent chaperone function and to provide protection from autolysis to aging bacteria. Targeted gene replacement was used to create a genetic knockout of the alpha crystallin protein in virulent MTB and the resulting strain shows dramatically decreased abilities in growth and replication in macrophage models of infection.