Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program.
Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program.
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DOI：
10.1084/jem.20030205
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发表时间：
2003-09-01
期刊：
影响因子：
--
通讯作者：
Schoolnik GK
中科院分区：
文献类型：
--
作者：
Voskuil MI;Schnappinger D;Visconti KC;Harrell MI;Dolganov GM;Sherman DR;Schoolnik GK
估计有20亿人潜伏感染结核分枝杆菌。探讨了启动和维持这种潜伏状态的宿主因素以及M.结核病在潜伏病变中的存活率是一个令人信服但尚未回答的问题。一种这样的宿主因子可以是一氧化氮（NO），一种表现出抗分枝杆菌特性的活化巨噬细胞的产物。NO的可能意义的证据来自结核病的小鼠模型，其显示在不能产生NO合酶的诱导型同种型的动物中和在用NO合酶抑制剂治疗的动物中的进行性感染。在这里，我们表明，O2和低，无毒浓度的NO竞争性地调节48基因的调节子，这是在体内表达，并准备在体外休眠的长期生存的杆菌的表达。发现NO可逆地抑制有氧呼吸和生长。含血红素的酶，可能是呼吸途径中的末端氧化酶，可能感测并整合NO和O2水平，并向调节子发出信号。这些数据导致一个模型，假设在肉芽肿，呼吸抑制NO的生产和O2限制限制M。潜伏性结核病患者的结核病复制率。
An estimated two billion persons are latently infected with Mycobacterium tuberculosis. The host factors that initiate and maintain this latent state and the mechanisms by which M. tuberculosis survives within latent lesions are compelling but unanswered questions. One such host factor may be nitric oxide (NO), a product of activated macrophages that exhibits antimycobacterial properties. Evidence for the possible significance of NO comes from murine models of tuberculosis showing progressive infection in animals unable to produce the inducible isoform of NO synthase and in animals treated with a NO synthase inhibitor. Here, we show that O2 and low, nontoxic concentrations of NO competitively modulate the expression of a 48-gene regulon, which is expressed in vivo and prepares bacilli for survival during long periods of in vitro dormancy. NO was found to reversibly inhibit aerobic respiration and growth. A heme-containing enzyme, possibly the terminal oxidase in the respiratory pathway, likely senses and integrates NO and O2 levels and signals the regulon. These data lead to a model postulating that, within granulomas, inhibition of respiration by NO production and O2 limitation constrains M. tuberculosis replication rates in persons with latent tuberculosis.
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巨噬细胞中结核分枝杆菌的转录适应：对吞噬体环境的见解。
影响因子：
15.3
作者：
Schnappinger, D;Ehrt, S;Voskuil, MI;Liu, Y;Mangan, JA;Monahan, IM;Dolganov, G;Efron, B;Butcher, PD;Nathan, C;Schoolnik, GK
通讯作者：
Schoolnik, GK
影响因子：
3.1
作者：
BOHNE, W;HEESEMANN, J;GROSS, U
通讯作者：
GROSS, U
影响因子：
64.5
作者：
Hausladen, A;Privalle, CT;Stamler, JS
通讯作者：
Stamler, JS
影响因子：
120.7
作者：
Dye, C;Scheele, S;Raviglione, RC
通讯作者：
Raviglione, RC
影响因子：
3.1
作者：
Rodriguez, GM;Voskuil, MI;Smith, I
通讯作者：
Smith, I