Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Division of Infectious Diseases, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University, Changwon, Republic of Korea.
Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Int J Antimicrob Agents. 2018 May;51(5):670-677. doi: 10.1016/j.ijantimicag.2017.12.019. Epub 2017 Dec 26.
The molecular mechanisms and characteristics of rifampicin (RIF) resistance in Staphylococcus epidermidis are poorly characterised, even though S. epidermidis is 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 in S. epidermidis. RIF-resistant mutants from two RIF-susceptible S. epidermidis strains (RP62A and IDRL-8883) were selected through in vitro and in vivo exposure to RIF. A total of 16 colonies with an RP62A background and 63 colonies with an IDRL-8883 background were analysed for rpoB mutations. 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 of rpoB. The following five amino acid substitutions were selected in vitro: Asp471→Asn; Asp471→Gly; Asp471→Val; Ser486→Tyr; and His481→Tyr. The following three amino acid substitutions were selected in vivo: His481→Tyr; Gln468→Lys; and Ser486→Phe. Asp471→Asn and Asp471→Gly changes were associated with susceptible minimal inhibitory concentrations (MICs). In vitro competition 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 several rpoB mutations in S. epidermidis.
表皮葡萄球菌中利福平（RIF）耐药的分子机制和特征尚未得到充分研究，尽管表皮葡萄球菌是与留置医疗设备相关感染有关的最常见的医院病原体之一。本研究旨在研究 RIF 耐药的演变，并对表皮葡萄球菌中相关的分子机制进行表征。通过体外和体内暴露于 RIF 从两种 RIF 敏感的表皮葡萄球菌（RP62A 和 IDRL-8883）中选择 RIF 耐药突变体。对 16 个具有 RP62A 背景的菌落和 63 个具有 IDRL-8883 背景的菌落进行 rpoB 突变分析。使用配对竞争测定和比较世代时间来评估 RIF 敏感和同源 RIF 耐药菌株的适应性。所有检测到的突变都位于 rpoB 的 I 簇中。体外选择了以下五个氨基酸取代：Asp471→Asn；Asp471→Gly；Asp471→Val；Ser486→Tyr；和 His481→Tyr。体内选择了以下三个氨基酸取代：His481→Tyr；Gln468→Lys；和 Ser486→Phe。Asp471→Asn 和 Asp471→Gly 变化与敏感最小抑菌浓度（MIC）相关。体外竞争测定表明，除了 Ser486→Tyr 和 Ser486→Phe 之外，所有 RIF 耐药突变体的相对适应性均<1.0。His481→Tyr 突变具有其自身的特定适应性成本和对生长速率的影响，而与菌株背景无关。总之，本研究介绍了表皮葡萄球菌中 rpoB 突变的分子特征和适应性成本。
