Control of Redox Balance by the Stringent Response Regulatory Protein Promotes Antioxidant Defenses of Salmonella
Control of Redox Balance by the Stringent Response Regulatory Protein Promotes Antioxidant Defenses of Salmonella
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DOI：
10.1074/jbc.m110.160960
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发表时间：
2010-11-19
影响因子：
4.8
通讯作者：
Vazquez-Torres, Andres
中科院分区：
文献类型：
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作者：
Henard, Calvin A.;Bourret, Travis J.;Vazquez-Torres, Andres
我们在此报告了严格反应调控的DnaK抑制蛋白（DksA）在抗氧化防御协调中的关键作用。DksA有助于微调谷胱甘肽生物合成基因的表达和戊糖磷酸途径和三羧酸循环中与还原力产生相关的离散步骤。DksA控制NAD(P)H/NAD(P)（+）氧化还原平衡为营养匮乏沙门氏菌下游抗氧化酶系统提供燃料。葡萄糖-6-磷酸脱氢酶编码基因zwf的条件表达，在DksA控制下，增加了DksA突变沙门氏菌的NADPH库和抗氧化防御能力。dksa介导的氧化还原平衡协调增强了固定相细菌的抗氧化防御能力。DksA不仅增加沙门氏菌对过氧化氢（H2O2）的抗性，而且在急性感染模型中，当暴露于NADPH吞噬细胞氧化酶产生的氧自由基时，它还促进了这种细胞内病原体的适应性。鉴于DksA在大多数遭受营养剥夺的细菌中调节基因表达的作用，我们的研究结果提出了一种可能性，即在系统发育不同的细菌物种中，通过这种调节蛋白控制中枢代谢途径来维持氧化还原稳态，这对抗氧化防御至关重要。
We report herein a critical role for the stringent response regulatory DnaK suppressor protein (DksA) in the coordination of antioxidant defenses. DksA helps fine-tune the expression of glutathione biosynthetic genes and discrete steps in the pentose phosphate pathway and tricarboxylic acid cycle that are associated with the generation of reducing power. Control of NAD(P)H/NAD(P)(+) redox balance by DksA fuels downstream antioxidant enzymatic systems in nutritionally starving Salmonella. Conditional expression of the glucose-6-phosphate dehydrogenase-encoding gene zwf, shown here to be under DksA control, increases both the NADPH pool and antioxidant defenses of dksA mutant Salmonella. The DksA-mediated coordination of redox balance boosts the antioxidant defenses of stationary phase bacteria. Not only does DksA increase resistance of Salmonella against hydrogen peroxide (H2O2), but it also promotes fitness of this intracellular pathogen when exposed to oxyradicals produced by the NADPH phagocyte oxidase in an acute model of infection. Given the role of DksA in the adjustment of gene expression in most bacteria undergoing nutritional deprivation, our findings raise the possibility that the control of central metabolic pathways by this regulatory protein maintains redox homeostasis essential for antioxidant defenses in phylogenetically diverse bacterial species.