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首页> 外文期刊>Infection and immunity >Protection of Mycobacterium tuberculosis from Reactive Oxygen Species Conferred by the mel2 Locus Impacts Persistence and Dissemination
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Protection of Mycobacterium tuberculosis from Reactive Oxygen Species Conferred by the mel2 Locus Impacts Persistence and Dissemination

机译：mel2基因座赋予的结核分枝杆菌免受活性氧影响持久性和传播

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摘要

Persistence of Mycobacterium tuberculosis in humans represents a major roadblock to elimination of tuberculosis. We describe identification of a locus in M. tuberculosis, mel2, that displays similarity to bacterial bioluminescent loci and plays an important role during persistence in mice. We constructed a deletion of the mel2 locus and found that the mutant displays increased susceptibility to reactive oxygen species (ROS). Upon infection of mice by aerosol the mutant grows normally until the persistent stage, where it does not persist as well as wild type. Histopathological analyses show that infection with the mel2 mutant results in reduced pathology and both CFU and histopathology indicate that dissemination of the mel2 mutant to the spleen is delayed. These data along with growth in activated macrophages and infection of Phox?/? and iNOS?/? mice and bone marrow-derived macrophages suggest that the primary mechanism by which mel2 affects pathogenesis is through its ability to confer resistance to ROS. These studies provide the first insight into the mechanism of action for this novel class of genes that are related to bioluminescence genes. The role of mel2 in resistance to ROS is important for persistence and dissemination of M. tuberculosis and suggests that homologues in other bacterial species are likely to play a role in pathogenesis.
机译：在人类中结核分枝杆菌的持续存在是消除结核病的主要障碍。我们描述了 M中一个基因座的鉴定。结核病mel2 ，与细菌生物发光基因座相似，并且在小鼠持久性中起重要作用。我们构建了一个 mel2 基因座的缺失，发现该突变体显示出对活性氧（ROS）的敏感性增加。气溶胶感染小鼠后，突变体正常生长直至持续阶段，在此阶段它不像野生型那样持久。组织病理学分析显示， mel2 突变体的感染导致病理学降低，CFU和组织病理学均表明 mel2 突变体向脾脏的传播被延迟。这些数据以及活化的巨噬细胞的生长以及Phox ？/？和iNOS ？/？小鼠以及骨髓来源的巨噬细胞的感染表明， > mel2 通过其对ROS的抵抗能力来影响发病机理。这些研究为这种与生物发光基因相关的新型基因的作用机理提供了第一个见识。 mel2 在抗ROS中的作用对于 M的持久性和传播很重要。结核病，并暗示其他细菌物种的同源物可能在发病机理中起作用。

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