Streptococcus mutans NADH Oxidase Lies at the Intersection of Overlapping Regulons Controlled by Oxygen and NAD+ Levels
Streptococcus mutans NADH Oxidase Lies at the Intersection of Overlapping Regulons Controlled by Oxygen and NAD+ Levels
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DOI：
10.1128/jb.01542-14
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发表时间：
2014-06-01
影响因子：
3.2
通讯作者：
Quivey, R. G., Jr.
中科院分区：
文献类型：
--
作者：
Baker, J. L.;Derr, A. M.;Quivey, R. G., Jr.
NADH氧化酶（Nox，由nox编码）是口腔病原体变形链球菌使用的含黄素的酶，用于将双原子氧还原为水，同时将NADH氧化为NAD。氮氧化物的关键性质是2倍：它用于再生NAD（+），碳循环代谢产物，并减少细胞内氧，防止形成破坏性的活性氧（ROS）。由于氧和NAD（+）已被证明分别调节全局转录因子Spx和雷克斯的活性，Nox可能处于两个应激调节子的关键连接点。在这项研究中，微阵列数据表明，无论是增加氧气或氮氧化物的损失导致改变参与能量代谢和运输的基因的表达和ROS代谢酶编码基因的上调。氮氧化物的损失也导致了几个编码转录因子和信号分子的基因的上调，包括氧化还原传感调节基因雷克斯。氮氧化物促进剂的表征表明，氮氧化物是由氧，通过SpxA，和雷克斯。这些数据表明了一个调节回路，其中nox在氧还原和NAD（+）再生中的作用分别影响Spx和雷克斯的活性水平，以及它们的调节子，这些调节子控制着对S.氧化应激条件下的变形菌。
NADH oxidase (Nox, encoded by nox) is a flavin-containing enzyme used by the oral pathogen Streptococcus mutans to reduce diatomic oxygen to water while oxidizing NADH to NAD. The critical nature of Nox is 2-fold: it serves to regenerate NAD(+), a carbon cycle metabolite, and to reduce intracellular oxygen, preventing formation of destructive reactive oxygen species (ROS). As oxygen and NAD(+) have been shown to modulate the activity of the global transcription factors Spx and Rex, respectively, Nox is potentially poised at a critical junction of two stress regulons. In this study, microarray data showed that either addition of oxygen or loss of nox resulted in altered expression of genes involved in energy metabolism and transport and the upregulation of genes encoding ROS-metabolizing enzymes. Loss of nox also resulted in upregulation of several genes encoding transcription factors and signaling molecules, including the redox-sensing regulator gene rex. Characterization of the nox promoter revealed that nox was regulated by oxygen, through SpxA, and by Rex. These data suggest a regulatory loop in which the roles of nox in reduction of oxygen and regeneration of NAD(+) affect the activity levels of Spx and Rex, respectively, and their regulons, which control several genes, including nox, crucial to growth of S. mutans under conditions of oxidative stress.