Enhanced resistance to erythromycin is conferred by the enterococcal msrC determinant in Staphylococcus aureus

Objectives: The msrC gene, found on the chromosome of Enterococcus faecium, shares a high degree of similarity with the staphylococcal erythromycin resistance determinant msr(A). The enterococcal determinant was cloned into Staphylococcus aureus to determine whether msrC could confer antibiotic resistance in staphylococci. Methods: A shuttle vector comprising pBluescript and pSK265 was used to introduce multiple copies of msrC into S. aureus RN4220. The integration vector pCL84 was employed to insert a single copy of msrC into the S. aureus chromosome. MICs were determined by the broth microdilution method. Results: Expression of msrC from both chromosomal and plasmid loci in erythromycin-susceptible S. aureus RN4220 (MIC 0.25 mg/L) gave rise to enhanced protection against erythromycin, with an MIC of 32-64 mg/L for S. aureus RN4220 containing msrC in multiple copies and an MIC of 16-64 mg/L with msrC inserted as a single copy in the S. aureus chromosome. Conclusions: MsrC mediates high-level resistance to erythromycin in S. aureus.