SpoVG Regulates Cell Wall Metabolism and Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus Strain N315

SpoVG Regulates Cell Wall Metabolism and Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus Strain N315
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SpoVG 调节耐甲氧西林金黄色葡萄球菌菌株 N315 的细胞壁代谢和苯唑西林耐药性

DOI:
10.1128/aac.00026-16
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发表时间:
2016-06-01
影响因子:
4.9
通讯作者:
Sun, Baolin
Sun, Baolin
中科院分区:
医学2区
文献类型:
--
作者:
Liu, Xiaoyu;Zhang, Shijie;Sun, Baolin

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越来越多的耐甲氧西林金黄色葡萄球菌(MRSA)菌株在健康个体中引起感染的病例引起了全世界的关注。MRSA菌株对几乎整个β-内酰胺类抗生素家族都有耐药性,这是由于获得了额外的青霉素结合蛋白PBP 2a。研究表明,spoVG参与苯唑西林耐药,但其调控机制仍不清楚。在本研究中,我们发现SpoVG通过促进MRSA菌株N315的细胞壁合成和抑制细胞壁降解在苯唑西林耐药性中起积极作用。在菌株N315中缺失spoVG导致苯唑西林抗性显著降低,同时Triton X-100诱导的自溶活性显著增加。实时荧光定量RT-PCR结果显示,spoVG突变体中与细胞壁代谢或苯唑西林抗性相关的8个基因的表达发生了改变。电泳迁移率变动分析表明,SpoVG可以直接结合到推定的启动子区的lytN(胞壁酶水解酶),femA,和lytSR(双组分系统)。这些发现表明SpoVG通过调节MRSA细胞壁代谢来调节苯唑西林耐药性的分子机制。
Increasing cases of infections caused by methicillin-resistant Staphylococcus aureus (MRSA) strains in healthy individuals have raised concerns worldwide. MRSA strains are resistant to almost the entire family of beta-lactam antibiotics due to the acquisition of an extra penicillin-binding protein, PBP2a. Studies have shown that spoVG is involved in oxacillin resistance, while the regulatory mechanism remains elusive. In this study, we have found that SpoVG plays a positive role in oxacillin resistance through promoting cell wall synthesis and inhibiting cell wall degradation in MRSA strain N315. Deletion of spoVG in strain N315 led to a significant decrease in oxacillin resistance and a dramatic increase in Triton X-100-induced autolytic activity simultaneously. Real-time quantitative reverse transcription-PCR revealed that the expression of 8 genes related to cell wall metabolism or oxacillin resistance was altered in the spoVG mutant. Electrophoretic mobility shift assay indicated that SpoVG can directly bind to the putative promoter regions of lytN (murein hydrolase), femA, and lytSR (the two-component system). These findings suggest a molecular mechanism in which SpoVG modulates oxacillin resistance by regulating cell wall metabolism in MRSA.