Rifampicin resistance in Staphylococcus epidermidis: molecular characterisation and fitness cost of rpoB mutations.
Rifampicin resistance in Staphylococcus epidermidis: molecular characterisation and fitness cost of rpoB mutations.
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DOI：
10.1016/j.ijantimicag.2017.12.019
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发表时间：
2017-12
影响因子：
10.8
通讯作者：
Y. Wi;K. Greenwood-Quaintance;C. Brinkman;Jean Y. H. Lee;B. Howden;Robin Patel
中科院分区：
文献类型：
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作者：
Y. Wi;K. Greenwood-Quaintance;C. Brinkman;Jean Y. H. Lee;B. Howden;Robin Patel
耐利福平（RIF）的表皮葡萄球菌的分子机制和特征尚不清楚。表皮病是与留置医疗器械相关感染相关的最常见的院内病原体之一。本研究的目的是研究RIF耐药性的演变，并描述相关的分子机制。epidermidis。两种rif易感基因的rif抗性突变体。通过体外暴露于RIF筛选表皮菌株（RP62A和IDRL-8883）。共分析了16个RP62A背景菌落和63个IDRL-8883背景菌落的rpob突变。利用配对竞争法和代数比较，评估了rif敏感菌株和等基因rif抗性菌株的适合度。所有检测到的突变都在rpob的簇I中。体外选择了以下5个氨基酸取代：Asp471→Asn；Asp471→g;Asp471→Val;Ser486→酪氨酸;和His481→酪氨酸。在体内选择了以下三个氨基酸取代：His481→Tyr；Gln468→赖氨酸;和Ser486→板式换热器。Asp471→Asn和Asp471→Gly变化与敏感最小抑制浓度（mic）相关。体外竞争分析显示，除Ser486→Tyr和Ser486→Phe外，所有抗rif突变体的相对适应度均<1.0。无论菌株背景如何，His481→Tyr突变都有其特定的适应成本和对生长速度的影响。总之，目前的研究提出了几种基因突变的分子特征和适应度成本。epidermidis。
The molecular mechanisms and characteristics of rifampicin (RIF) resistance inStaphylococcus epidermidisare poorly characterised, even thoughS. epidermidisis one of the most common nosocomial pathogens associated with indwelling medical device-related infections. The aim of this study was to investigate the evolution of RIF resistance and to characterise the associated molecular mechanisms inS. epidermidis. RIF-resistant mutants from two RIF-susceptibleS. epidermidisstrains (RP62A and IDRL-8883) were selected throughin vitroandin vivoexposure to RIF. A total of 16 colonies with an RP62A background and 63 colonies with an IDRL-8883 background were analysed forrpoBmutations. The fitness of RIF-susceptible and isogenic RIF-resistant strains was assessed using a paired competition assay and by comparing generation times. All mutations detected were in cluster I ofrpoB. The following five amino acid substitutions were selectedin vitro: Asp471→Asn; Asp471→Gly; Asp471→Val; Ser486→Tyr; and His481→Tyr. The following three amino acid substitutions were selectedin vivo: His481→Tyr; Gln468→Lys; and Ser486→Phe. Asp471→Asn and Asp471→Gly changes were associated with susceptible minimal inhibitory concentrations (MICs).In vitrocompetition assays revealed that all RIF-resistant mutants other than Ser486→Tyr and Ser486→Phe had a relative fitness of <1.0. His481→Tyr mutations had their own specific fitness costs and effects on growth rate, irrespective of strain background. In conclusion, the current study presents molecular characterisations and fitness costs of severalrpoBmutations inS. epidermidis.