Rv3303c of Mycobacterium tuberculosis protects tubercle bacilli against oxidative stress in vivo and contributes to virulence in mice
Rv3303c of Mycobacterium tuberculosis protects tubercle bacilli against oxidative stress in vivo and contributes to virulence in mice
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DOI：
10.1016/j.micinf.2006.09.004
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发表时间：
2006-11-01
影响因子：
5.8
通讯作者：
Srivastava, Ranjana
中科院分区：
文献类型：
--
作者：
Akhtar, Parvez;Srivastava, S.;Srivastava, Ranjana
结核分枝杆菌在体内氧化应激下的生存能力是致病的一个重要方面。Rv3303c基因来自M.结核杆菌编码NAD（P）H醌还原酶。这些酶已被证明可以管理其他病原菌中的氧化应激。我们假设Rv3303c蛋白将清除宿主释放的活性氧，从而减少对M的氧化应激。结核rv3303c被PCR克隆，并且纯化的重组酶还原超氧化物产生剂甲萘醌。将rv3303c的反义和正义RNA构建体在M.结核病H37Rv.转化子的特征在于特异性mRNA和蛋白质的表达差异。与有义转化体相比，反义转化体的毒力显著降低，如通过几个参数如感染小鼠的重量和存活、体内生长、定殖和肺的组织病理学来判断。在甲萘醌存在下，正义反义寡核苷酸比反义反义寡核苷酸对体外杀伤的抗性更强。因此，rv3303c基因可能与M.结核病在体内的作用，这可能部分是通过增加对活性氧中间体的抗性从而增强细胞内生长和定殖来介导的。(c)2006年，Elsevier Masson SAS。All rights reserved.
Ability of Mycobacterium tuberculosis to survive under oxidative stress in vivo is an important aspect of pathogenesis. Rv3303c gene from M. tuberculosis encodes an NAD(P)H quinone reductase. These enzymes have been shown to manage oxidative stress in other pathogenic bacteria. We have hypothesized that Rv3303c protein will remove reactive oxygen species released by the host and hence reduce oxidative stress to M. tuberculosis. rv3303c was PCR cloned and the purified recombinant enzyme reduced superoxide generator menadione. Antisense and sense RNA constructs of rv3303c were electroporated in M. tuberculosis H37Rv. The transformants were characterized by difference in expression of specific mRNA and protein. Antisense transformants were markedly reduced in virulence as compared to sense transformants as judged by several parameters such as weight and survival of infected mice, growth in vivo, colonization and histopathology of lungs. In the presence of menadione, the sense transformant was more resistant to killing in vitro than the antisense transformant. It may be concluded that the rv3303c gene contributes to virulence of M. tuberculosis in vivo and this might be mediated in part by increased resistance to reactive oxygen intermediates thereby enhancing intracellular growth and colonization. (c) 2006 Elsevier Masson SAS. All rights reserved.