Novel mechanism for plasmid-mediated erythromycin resistance by pNE24 from Staphylococcus epidermidis

Abstract

We describe an unusual type of erythromycin resistance (Emr) mediated by a plasmid designated pNE24 from Staphylococcus epidermidis. This 26.5-kilobase plasmid encodes resistance strictly to 14-membered macrolide antibiotics, erythromycin, and oleandomycin. Resistance to other macrolide-lincosamide-streptogramin B (MLS) antibiotics was not observed even after a prior induction stimulus with various MLS antibiotics. Plasmid pNE24 was found to express resistance constitutively and manifested a low to intermediate MIC (62.5 micrograms/ml) for erythromycin. The resistance gene, designated erpA, appears to mediate resistance by altering the permeability of the host cell for erythromycin, because the measured uptake of 14C-labeled erythromycin by strain 958-2 (containing pNE24) was lower than for the erythromycin-susceptible, isogenic strain 958-1. No inactivation of erythromycin in overnight broth culture supernatants could be detected. In addition, no significant loss in binding affinity between [14C]erythromycin and ribosome could be detected for ribosomes isolated from strain 958-2 relative to 958-1, indicating that pNE24 probably does not produce a modification of the bacterial ribosome. No other selectable marker was found associated with pNE24; however, a 60,000-dalton protein was present only in the membrane fractions of cells (958-2) containing pNE24 and may play a role in mediating resistance to erythromycin.