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Contribution of NADH oxidase to oxidative stress tolerance and virulence of Streptococcus suis serotype 2.

ABSTRACT: Streptococcus suis is a major swine and zoonotic pathogen that causes severe infections. Previously, we identified 2 Spx regulators in S. suis, and demonstrated that SpxA1 affects oxidative stress tolerance and virulence. However, the mechanism behind SpxA1 function remains unclear. In this study, we targeted 4 genes that were expressed at significantly reduced levels in the spxA1 mutant, to determine their specific roles in adaptation to oxidative stress and virulence potential. The ?nox strain exhibited impaired growth under oxidative stress conditions, suggesting that NADH oxidase is involved in oxidative stress tolerance. Using murine and pig infection models, we demonstrate for the first time that NADH oxidase is required for virulence in S. suis 2. Furthermore, the enzymatic activity of NADH oxidase has a key role in oxidative stress tolerance and a secondary role in virulence. Collectively, our findings reveal that NADH oxidase plays an important part in SpxA1 function and provide a new insight into the pathogenesis of S. suis 2.

SUBMITTER: Zheng C

PROVIDER: S-EPMC5963199 | biostudies-other | 2017 Jan

REPOSITORIES: biostudies-other

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Contribution of NADH oxidase to oxidative stress tolerance and virulence of Streptococcus suis serotype 2.

Zheng Chengkun C Ren Sujing S Xu Jiali J Zhao Xigong X Shi Guolin G Wu Jianping J Li Jinquan J Chen Huanchun H Bei Weicheng W

Virulence 20160617 1

Streptococcus suis is a major swine and zoonotic pathogen that causes severe infections. Previously, we identified 2 Spx regulators in S. suis, and demonstrated that SpxA1 affects oxidative stress tolerance and virulence. However, the mechanism behind SpxA1 function remains unclear. In this study, we targeted 4 genes that were expressed at significantly reduced levels in the spxA1 mutant, to determine their specific roles in adaptation to oxidative stress and virulence potential. The Δnox strain ...[more]

PMID: 27315343

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Project description:BackgroundThe S. mutans LrgA/B holin-like proteins have been shown to affect biofilm formation and oxidative stress tolerance, and are regulated by oxygenation, glucose levels, and by the LytST two-component system. In this study, we sought to determine if LytST was involved in regulating lrgAB expression in response to glucose and oxygenation in S. mutans.ResultsReal-time PCR revealed that growth phase-dependent regulation of lrgAB expression in response to glucose metabolism is mediated by LytST under low-oxygen conditions. However, the effect of LytST on lrgAB expression was less pronounced when cells were grown with aeration. RNA expression profiles in the wild-type and lytS mutant strains were compared using microarrays in early exponential and late exponential phase cells. The expression of 40 and 136 genes in early-exponential and late exponential phase, respectively, was altered in the lytS mutant. Although expression of comYB, encoding a DNA binding-uptake protein, was substantially increased in the lytS mutant, this did not translate to an effect on competence. However, a lrgA mutant displayed a substantial decrease in transformation efficiency, suggestive of a previously-unknown link between LrgA and S. mutans competence development. Finally, increased expression of genes encoding antioxidant and DNA recombination/repair enzymes was observed in the lytS mutant, suggesting that the mutant may be subjected to increased oxidative stress during normal growth. Although the intracellular levels of reaction oxygen species (ROS) appeared similar between wild-type and lytS mutant strains after overnight growth, challenge of these strains with hydrogen peroxide (H2O2) resulted in increased intracellular ROS in the lytS mutant.ConclusionsOverall, these results: (1) Reinforce the importance of LytST in governing lrgAB expression in response to glucose and oxygen, (2) Define a new role for LytST in global gene regulation and resistance to H2O2, and (3) Uncover a potential link between LrgAB and competence development in S. mutans.

Dataset Information

Contribution of NADH oxidase to oxidative stress tolerance and virulence of Streptococcus suis serotype 2.

Publications

Contribution of NADH oxidase to oxidative stress tolerance and virulence of Streptococcus suis serotype 2.

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