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首页> 外文期刊>Infection and immunity >The Staphylococcus aureus Two-Component Regulatory System, GraRS, Senses and Confers Resistance to Selected Cationic Antimicrobial Peptides
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The Staphylococcus aureus Two-Component Regulatory System, GraRS, Senses and Confers Resistance to Selected Cationic Antimicrobial Peptides

机译：金黄色葡萄球菌两组分调节系统，GraRS，感官和赋予对选定的阳离子抗菌肽的耐药性

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The two-component regulatory system, GraRS, appears to be involved in staphylococcal responses to cationic antimicrobial peptides (CAPs). However, the mechanism(s) by which GraRS is induced, regulated, and modulated remain undefined. In this study, we used two well-characterized MRSA strains (Mu50 and COL) and their respective mutants of graR and vraG (encoding the ABC transporter-dependent efflux pump immediately downstream of graRS), and show that (i) the expression of two key determinants of net positive surface charge (mprF and dlt) is dependent on the cotranscription of both graR and vraG, (ii) reduced expression of mprF and dlt in graR mutants was phenotypically associated with reduced surface-positive charge, (iii) this net reduction in surface-positive charge in graR and vraG mutants, in turn, correlated with enhanced killing by a range of CAPs of diverse structure and origin, including those from mammalian platelets (tPMPs) and neutrophils (hNP-1) and from bacteria (polymyxin B), and (iv) the synthesis and translocation of membrane lysyl-phosphatidylglycerol (an mprF-dependent function) was substantially lower in graR and vraG mutants than in parental strains. Importantly, the inducibility of mprF and dlt transcription via the graRS-vraFG pathway was selective, with induction by sublethal exposure to the CAPs, RP-1 (platelets), and polymyxin B, but not by other cationic molecules (hNP-1, vancomycin, gentamicin, or calcium-daptomycin). Although graR regulates expression of vraG, the expression of graR was codependent on an intact downstream vraG locus. Collectively, these data support an important role of the graRS and vraFG loci in the sensing of and response to specific CAPs involved in innate host defenses.
机译：两组分的调节系统GraRS似乎参与了对阳离子抗菌肽（CAP）的葡萄球菌反应。但是，诱导，调控和调节GraRS的机制仍然不确定。在这项研究中，我们使用了两个特征明确的MRSA菌株（Mu50和COL）及其各自的 graR 和 vraG 突变体（在下游直接编码ABC转运蛋白依赖性外排泵） ，并证明（i）净正表面电荷的两个关键决定因素（ mprF 和 dlt ）的表达取决于 graR 和 vraG 的共转录，（ii）降低 graR中 mprF 和 dlt 的表达突变体与减少的表面阳性电荷在表型上相关，（iii）在 graR 和 vraG 突变体中，表面阳性电荷的净减少与之相关可以通过多种结构和来源的CAP增强杀伤力，包括来自哺乳动物血小板（tPMPs）和中性粒细胞（hNP-1）以及来自细菌（多粘菌素B）的CAP，以及（iv）膜赖氨酰磷脂酰甘油的合成和转运（与 mprF 有关的函数）是在 graR 和 vraG 突变体中比在亲本菌株中要低得多。重要的是，通过 graRS-vraFG 途径的 mprF 和 dlt 转录的诱导能力是选择性的，亚致死性暴露于CAP，RP- 1（血小板）和多粘菌素B，但不受其他阳离子分子（hNP-1，万古霉素，庆大霉素或达托霉素钙）的影响。尽管 graR 调节 vraG 的表达，但 graR 的表达却与完整的下游 vraG 基因座相关。这些数据共同支持 graRS 和 vraFG 基因座在先天宿主防御中涉及的特定CAP的感知和响应中的重要作用。

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