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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Spontaneous deletion of the methicillin resistance determinant, mecA, partially compensates for the fitness cost associated with high-level vancomycin resistance in Staphylococcus aureus.
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Spontaneous deletion of the methicillin resistance determinant, mecA, partially compensates for the fitness cost associated with high-level vancomycin resistance in Staphylococcus aureus.

机译：自发删除甲氧西林耐药性决定因素mecA，部分补偿了金黄色葡萄球菌对高水平万古霉素耐药性的适应性费用。

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摘要

Treatment of infections caused by Staphylococcus aureus is often confounded by the bacterium's ability to develop resistance to chemotherapeutic agents. Methicillin-resistant S. aureus (MRSA) arises through the acquisition of staphylococcal chromosomal cassette mec (SCCmec), a genomic island containing the methicillin resistance determinant, mecA. In contrast, resistance to vancomycin can result from exposure to the drug, a mechanism that is not dependent upon a gene acquisition event. Here we describe three MRSA strains that became resistant to vancomycin during passage in the presence of increasing concentrations of the drug. In each case two derivative strains were isolated, one that had lost mecA and one that retained mecA during passage. Strain 5836VR lost mecA by the site-specific chromosomal excision of SCCmec, while the other two strains (strains 3130VR and VP32) deleted portions of their SCCmec elements in a manner that appeared to involve IS431. Conversion to vancomycin resistance caused a decrease in the growth rate that was partially compensated for by the deletion of mecA. In mixed-culture competition experiments, vancomycin-resistant strains that lacked mecA readily outcompeted their mecA-containing counterparts, suggesting that the loss of mecA during conversion to vancomycin resistance was advantageous to the organism.
机译：由金黄色葡萄球菌引起的感染的治疗常常被细菌对化学治疗剂产生抗性的能力所混淆。耐甲氧西林的金黄色葡萄球菌（MRSA）是通过获取葡萄球菌染色体盒mec（SCCmec）而获得的，该基因组岛包含甲氧西林抗性决定簇mecA。相反，对万古霉素的抗药性可能是由于接触该药物而引起的，该机制不依赖于基因获取事件。在这里，我们描述了三种MRSA菌株，它们在药物浓度不断升高的情况下在传代过程中对万古霉素具有抗性。在每种情况下，分离出两种衍生菌株，一种在传代过程中丢失了mecA，另一种则保留了mecA。 5836VR菌株通过SCCmec的位点特异性染色体切除而失去了mecA，而其他两个菌株（3130VR和VP32菌株）以似乎涉及IS431的方式删除了其SCCmec元件的部分。转化为万古霉素耐药性导致生长速率下降，这部分被mecA缺失所弥补。在混合培养竞争实验中，缺乏mecA的耐万古霉素的菌种比其含mecA的菌种更容易胜过竞争，这表明在转化为万古霉素抗性的过程中mecA的丧失对有机体有利。

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