Daptomycin selects for genetic and phenotypic adaptations leading to antibiotic tolerance in MRSA
Daptomycin selects for genetic and phenotypic adaptations leading to antibiotic tolerance in MRSA
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DOI：
10.1093/jac/dky148
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发表时间：
2018-08-01
影响因子：
5.2
通讯作者：
Rose, Warren E.
中科院分区：
文献类型：
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作者：
Berti, Andrew D.;Shukla, Neehal;Rose, Warren E.
目的：金黄色葡萄球菌对达托霉素不敏感可以通过单个或多个突变的积累而出现，每个突变都会导致达托霉素 MIC 略有增加。达托霉素不敏感表型可以包括其他特征，例如达托霉素耐受性。本研究鉴定了金黄色葡萄球菌基因组区域，这些区域在长期接触达托霉素后经常发生突变，但之前并未与达托霉素不敏感性相关。 方法：将金黄色葡萄球菌 J01 在达托霉素中平行连续传代 28 天后独立观察到的相同 8 个基因座的序列变异被单独引入金黄色葡萄球菌 J01。通过微肉汤稀释来测定 MIC。通过杀伤曲线分析确定达托霉素的杀伤力和耐受性。结果：snoF、hmp1、sspA、rimP、hepT、rsh、map1 和 amaP 中的单一突变对达托霉素 MIC 的影响不大（
Objectives: Daptomycin non-susceptibility in Staphylococcus aureus can emerge via the accumulation of single or multiple mutations, each resulting in a slight increase in the daptomycin MIC. The daptomycin-non-susceptible phenotype may include other features such as daptomycin tolerance. This study identifies S. aureus genomic regions that frequently develop mutations following prolonged daptomycin exposure but have not been previously associated with daptomycin non-susceptibility.Methods: Sequence variations in the same eight loci independently observed following 28 day parallel serial passages of S. aureus J01 in daptomycin were introduced in isolation into S. aureus J01. MICs were determined by microbroth dilution. Daptomycin killing and tolerance were determined by kill curve analysis.Results: Single mutations in snoF, hmp1, sspA, rimP, hepT, rsh, map1 and amaP had only a modest impact on the daptomycin MIC (