ACTIVATION BY NITRIC-OXIDE OF AN OXIDATIVE-STRESS RESPONSE THAT DEFENDS ESCHERICHIA-COLI AGAINST ACTIVATED MACROPHAGES
ACTIVATION BY NITRIC-OXIDE OF AN OXIDATIVE-STRESS RESPONSE THAT DEFENDS ESCHERICHIA-COLI AGAINST ACTIVATED MACROPHAGES
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DOI：
10.1073/pnas.90.21.9993
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发表时间：
1993-11-01
影响因子：
11.1
通讯作者：
DEMPLE, B
中科院分区：
文献类型：
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作者：
NUNOSHIBA, T;DEROJASWALKER, T;DEMPLE, B
一氧化氮是一种自由基（NO）。生物学上通过一氧化氮合酶氧化L-精氨酸而形成。NO.在哺乳动物细胞中瞬时产生，用于细胞间信号传导，并大量产生，引起细胞停滞和细胞毒性。在后一种情况下，NO.是活化的巨噬细胞的故意细胞毒性产物，沿着其他活性氧物质，如过氧化氢（H2 O2）和超氧化物（O2.-）。大肠杆菌对H2 O2和O2有一套复杂的反应。这涉及几乎等于80诱导蛋白质;我们想知道这些细菌是否可能诱导类似的防御一氧化氮。我们在这里表明，由氧化还原敏感的转录调节因子SoxR控制的多基因系统被NO激活。这种诱导赋予细菌对活化的鼠巨噬细胞的抗性，其动力学与这些细胞产生NO平行。消除特定的SoxR调节基因减少了这些细菌对细胞毒性巨噬细胞的抗性。所需的功能包括含锰超氧化物歧化酶，内切酶IV（一种氧化损伤的DNA修复酶）和micF，外膜孔蛋白OmpF的反义调节剂。这些结果表明，SoxR是细胞暴露于NO的传感器，并且soxRS应答系统可能有助于细菌毒力。
Nitric oxide is a free radical (NO.) formed biologically through the oxidation Of L-arginine by nitric oxide synthases. NO. is produced transiently in mammalian cells for intercellular signaling and in copious quantities to cause cytostasis and cytotoxicity. In the latter situation, NO. is a deliberate cytotoxic product of activated macrophages, along with other reactive oxygen species such as hydrogen peroxide (H2O2) and superoxide (O2.-). Escherichia coli has a complex set of responses to H2O2 and O2.- that involves almost-equal-to 80 inducible proteins; we wondered whether these bacteria might induce analogous defenses against nitric oxide. We show here that a multigene system controlled by the redox-sensitive transcriptional regulator SoxR is activated by NO. in vivo. This induction confers bacterial resistance to activated murine macrophages with kinetics that parallel the production of NO. by these cells. Elimination of specific SoxR-regulated genes diminishes the resistance of these bacteria to the cytotoxic macrophages. The required functions include manganese-containing superoxide dismutase, endonudease IV (a DNA-repair enzyme for oxidative damage), and micF, an antisense regulator of the outer membrane porin OmpF. These results demonstrate that SoxR is a sensor for cellular exposure to NO., and that the soxRS response system may contribute to bacterial virulence.