The Staphylococcus aureus AirSR Two-Component System Mediates Reactive Oxygen Species Resistance via Transcriptional Regulation of Staphyloxanthin Production
The Staphylococcus aureus AirSR Two-Component System Mediates Reactive Oxygen Species Resistance via Transcriptional Regulation of Staphyloxanthin Production
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DOI：
10.1128/iai.00838-16
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发表时间：
2017-02-01
影响因子：
3.1
通讯作者：
Ji, Yinduo
中科院分区：
文献类型：
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作者：
Hall, Jeffrey W.;Yang, Junshu;Ji, Yinduo
金黄色葡萄球菌是一种重要的机会致病菌，是许多医院和社区获得性感染的病原。金黄色葡萄球菌菌落的金黄色色素葡萄黄质使其区别于其他葡萄球菌和相关的革兰氏阳性球菌。葡萄黄质是一系列生物合成步骤的产物，产生独特的膜包埋C-30金类胡萝卜素，是一种重要的抗氧化剂。我们观察到，在有氧培养条件下，与野生型菌株相比，具有可诱导的airR过表达盒的菌株的葡萄黄质产量明显增加。进一步分析表明，AirR反应调节因子的缺失或过量产生分别导致葡萄黄质产量和过氧化氢杀伤敏感性的相应减少或增加。此外，在全血生存试验中，在AirR过度产生过程中葡萄黄质的遗传消除消除了葡萄黄质产生增加的保护性表型。启动子报告子和凝胶移位实验确定，AirR反应调节因子是葡萄黄素-生物合成操纵子crtOPQMN的直接正调控因子，但对备选sigma因子b具有上位性。综上所述，这些数据表明，AirR正调控葡萄黄素-生物合成操纵子crtOPQMN，促进金黄色葡萄球菌在氧化剂存在下的存活。
Staphylococcus aureus is an important opportunistic pathogen and is the etiological agent of many hospital-and community-acquired infections. The golden pigment, staphyloxanthin, of S. aureus colonies distinguishes it from other staphylococci and related Gram-positive cocci. Staphyloxanthin is the product of a series of biosynthetic steps that produce a unique membrane-embedded C-30 golden carotenoid and is an important antioxidant. We observed that a strain with an inducible airR overexpression cassette had noticeably increased staphyloxanthin production compared to the wild-type strain under aerobic culturing conditions. Further analysis revealed that depletion or overproduction of the AirR response regulator resulted in a corresponding decrease or increase in staphyloxanthin production and susceptibility to killing by hydrogen peroxide, respectively. Furthermore, the genetic elimination of staphyloxanthin during AirR overproduction abolished the protective phenotype of increased staphyloxanthin production in a whole-blood survival assay. Promoter reporter and gel shift assays determined that the AirR response regulator is a direct positive regulator of the staphyloxanthin-biosynthetic operon, crtOPQMN, but is epistatic to alternative sigma factor B. Taken together, these data indicate that AirSR positively regulates the staphyloxanthin-biosynthetic operon crtOPQMN, promoting survival of S. aureus in the presence of oxidants.