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Rifampicin resistance in Staphylococcus epidermidis: molecular characterisation and fitness cost of rpoB mutations.

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: 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.

journal_name

Int J Antimicrob Agents

journal_title

International journal of antimicrobial agents

authors

Wi YM,Greenwood-Quaintance KE,Brinkman CL,Lee JYH,Howden BP,Patel R

doi

10.1016/j.ijantimicag.2017.12.019

subject

Has Abstract

pub_date

2018-05-01 00:00:00

pages

670-677

issue

5

eissn

0924-8579

issn

1872-7913

pii

S0924-8579(17)30453-3

journal_volume

51

pub_type

杂志文章

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