Associations between resistance phenotype and gene expression in response to serial exposure to oxacillin and ciprofloxacin in Staphylococcus aureus

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Abstract

This study was designed to delineate the relationship between resistance phenotypes and gene expression in wild-type (SAWT), oxacillin-induced (SAOXA), ciprofloxacin-induced (SACIP) and clinically acquired antibiotic-resistant Staphylococcus aureus (SACA) exposed to oxacillin (β-lactam) and ciprofloxacin (fluoroquinolone). The phenotypic response and gene expression were varied with the antibiotic exposure. SAWT was highly resistant to oxacillin (MIC = 8 μg ml−1) after serial exposure to oxacillin, while the oxacillin susceptibility was not changed in SAWT when exposed to ciprofloxacin (MIC = 0·25 μg ml−1). The clinical isolate, SACA, was highly resistant to all classes of antibiotics used in this study. The increased resistance of SAOXA and SACIP to penicillinase-labile penicillins was attributed to the production of β-lactamase, which is in good agreement with the overexpression of blaZ (>2-fold). The overexpression of efflux pump-related genes (norA, norB, norC, mdeA, mepR, mgrA and lmrS) was associated with the increased resistance of SACIP and SACA to aminoglycosides and quinolones. This study confirmed that the linkage between resistance phenotypes and molecular genotypes highly varied depending on intrinsic resistance profile, response to antibiotic exposure and genes conferring resistance. This study provides useful information for understanding the mechanisms of methicillin resistance in S. aureus in association with phenotypic and genotypic resistance determinants.

Significance and Impact of the Study:

The improvement in current standards is essential to accurately detect methicillin-resistant Staphylococcus aureus in consideration of various resistance phenotypes and genotypes. The varied and distinctive expression patterns of antibiotic resistance-related genes were observed in S. aureus exposed to oxacillin and ciprofloxacin. It is worth noting the relationship between resistance phenotype and resistance genotype in terms of MIC values and expression of antibiotic resistance determinants. This study provides useful information for understanding the mechanisms of methicillin resistance in S. aureus in association with phenotypic and genotypic resistance determinants.

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