The proteasome of Mycobacterium tuberculosis is required for resistance to nitric oxide
The proteasome of Mycobacterium tuberculosis is required for resistance to nitric oxide
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DOI：
10.1126/science.1091176
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发表时间：
2003-12-12
期刊：
影响因子：
56.9
通讯作者：
Nathan, CF
中科院分区：
文献类型：
--
作者：
Darwin, KH;Ehrt, S;Nathan, CF
巨噬细胞产生一氧化氮和其他活性氮中间体（RNI）有助于控制结核分枝杆菌（Mtb）的感染。然而，保护不完善，感染持续存在。为了鉴定Mtb抵抗RNI所需的基因，我们筛选了10，100个Mtb转座子突变体对酸化亚硝酸盐的高敏感性。我们发现了12个突变体，其中7个基因插入了6条途径，包括DNA修复（uvrB）和黄素辅因子（fbiC）的合成。5个突变体在蛋白酶体相关基因中有插入。一个假定的蛋白酶体腺苷三磷酸酶缺陷的结核分枝杆菌突变体在小鼠中减弱，暴露于蛋白酶体蛋白酶抑制剂显着敏感的野生型结核分枝杆菌RNI。因此，分枝杆菌蛋白酶体作为一种防御氧化或亚硝化应激。
The production of nitric oxide and other reactive nitrogen intermediates (RNI) by macrophages helps to control infection by Mycobacterium tuberculosis (Mtb). However, the protection is imperfect and infection persists. To identify genes that Mtb requires to resist RNI, we screened 10,100 Mtb transposon mutants for hypersusceptibility to acidified nitrite. We found 12 mutants with insertions in seven genes representing six pathways, including the repair of DNA (uvrB) and the synthesis of a flavin cofactor (fbiC). Five mutants had insertions in proteasome-associated genes. An Mtb mutant deficient in a presumptive proteasomal adenosine triphosphatase was attenuated in mice, and exposure to proteasomal protease inhibitors markedly sensitized wild-type Mtb to RNI. Thus, the mycobacterial proteasome serves as a defense against oxidative or nitrosative stress.