Regulatory Requirements for Staphylococcus aureus Nitric Oxide Resistance
Regulatory Requirements for Staphylococcus aureus Nitric Oxide Resistance
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DOI：
10.1128/jb.00229-16
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发表时间：
2016-08-01
影响因子：
3.2
通讯作者：
Richardson, Anthony R.
中科院分区：
文献类型：
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作者：
Grosser, Melinda R.;Weiss, Andy;Richardson, Anthony R.
金黄色葡萄球菌抵抗宿主天然免疫的能力增加了其发病机制的严重性和普遍性。一氧化氮（NO中心点）是一种先天性免疫自由基，对于有效清除各种微生物病原体至关重要。微生物暴露于NO中心点通常导致生长抑制和应激调节子的诱导。S.然而，金黄色葡萄球菌响应于NO中心点诱导代谢状态，其允许持续复制并排除应激调节子诱导。调节这种独特反应的调节因素在很大程度上仍不明确。在这里，我们采用了一个有针对性的转座子筛选和转录组学，以确定和表征五个调节子的NO中心点阻力在S。金黄色：三种以前与NO中心点抗性无关的毒力调节子SarA、CodY和Rot，以及两种具有确定作用的调节子Fur和SrrAB。我们提供了新的见解Fur和SrrAB在NO中心点应力的贡献，并表明S。金黄色葡萄球菌Δ sarA突变体，最敏感的新发现的突变体，表现出代谢功能障碍和广泛的转录失调后，NO中心点曝光。总之，我们的研究结果广泛地表征了S.的金黄色葡萄球菌，并提出了一个有趣的重叠之间的监管NO中心点的阻力和毒力在这个良好适应的人类pathogen.IMPORTANCEThe多产的人类病原体金黄色葡萄球菌是唯一能够抵抗抗微生物自由基一氧化氮（NO中心点），先天免疫反应的重要组成部分。然而，一个完整的理解如何S。金黄色葡萄球菌调节NO中心点的有效反应缺乏。在这里，我们涉及三个中央毒力调节因子，SarA，CodY和Rot，作为S。金黄色葡萄球菌NO中心点反应。此外，我们阐述了两个监管机构，SrrAB和Fur，已经知道在S。金黄色葡萄球菌NO中心点抗性。我们的研究揭示了S.金黄色葡萄球菌的致病性，并表明，转录反应的S。金黄色葡萄球菌对NO中心点具有高度多效性，并且与代谢和毒力调节内在相关。
The ability of Staphylococcus aureus to resist host innate immunity augments the severity and pervasiveness of its pathogenesis. Nitric oxide (NO center dot) is an innate immune radical that is critical for the efficient clearance of a wide range of microbial pathogens. Exposure of microbes to NO center dot typically results in growth inhibition and induction of stress regulons. S. aureus, however, induces a metabolic state in response to NO center dot that allows for continued replication and precludes stress regulon induction. The regulatory factors mediating this distinctive response remain largely undefined. Here, we employ a targeted transposon screen and tran-scriptomics to identify and characterize five regulons essential for NO center dot resistance in S. aureus: three virulence regulons not formerly associated with NO center dot resistance, SarA, CodY, and Rot, as well as two regulons with established roles, Fur and SrrAB. We provide new insights into the contributions of Fur and SrrAB during NO center dot stress and show that the S. aureus Delta sarA mutant, the most sensitive of the newly identified mutants, exhibits metabolic dysfunction and widespread transcriptional dysregulation following NO center dot exposure. Altogether, our results broadly characterize the regulatory requirements for NO center dot resistance in S. aureus and suggest an intriguing overlap between the regulation of NO center dot resistance and virulence in this well-adapted human pathogen.IMPORTANCEThe prolific human pathogen Staphylococcus aureus is uniquely capable of resisting the antimicrobial radical nitric oxide (NO center dot), a crucial component of the innate immune response. However, a complete understanding of how S. aureus regulates an effective response to NO center dot is lacking. Here, we implicate three central virulence regulators, SarA, CodY, and Rot, as major players in the S. aureus NO center dot response. Additionally, we elaborate on the contribution of two regulators, SrrAB and Fur, already known to play a crucial role in S. aureus NO center dot resistance. Our study sheds light on a unique facet of S. aureus pathogenicity and demonstrates that the transcriptional response of S. aureus to NO center dot is highly pleiotropic and intrinsically tied to metabolism and virulence regulation.