Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8738530 | International Journal of Antimicrobial Agents | 2018 | 26 Pages |
Abstract
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: Asp471âAsn; Asp471âGly; Asp471âVal; Ser486âTyr; and His481âTyr. The following three amino acid substitutions were selected in vivo: His481âTyr; Gln468âLys; and Ser486âPhe. Asp471âAsn and Asp471âGly changes were associated with susceptible minimal inhibitory concentrations (MICs). In vitro competition assays revealed that all RIF-resistant mutants other than Ser486âTyr and Ser486âPhe had a relative fitness of <1.0. His481âTyr 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.
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Authors
Yu Mi Wi, Kerryl E. Greenwood-Quaintance, Cassandra L. Brinkman, Jean Y.H. Lee, Benjamin P. Howden, Robin Patel,