MupB, a New High-Level Mupirocin Resistance Mechanism in Staphylococcus aureus

Abstract

ABSTRACTMupirocin is a topical antibiotic used for the treatment of skin infections and the eradication of methicillin-resistantStaphylococcus aureuscarriage. It inhibits bacterial protein synthesis by interfering with isoleucyl-tRNA synthetase activity. High-level mupirocin resistance (MIC of ≥512 μg/ml) is mediated by the expression ofmupA(ileS2), which encodes an alternate isoleucyl-tRNA synthetase. In this study, we describe high-level mupirocin resistance mediated by a novel locus,mupB. ThemupBgene (3,102 bp) shares 65.5% sequence identity withmupAbut only 45.5% identity withileS. The deduced MupB protein shares 58.1% identity (72.3% similarity) and 25.4% identity (41.8% similarity) with MupA and IleS, respectively. Despite this limited homology, MupB contains conserved motifs found in class I tRNA synthetases. Attempts to transfer high-level mupirocin resistance via conjugation or transformation (using plasmid extracts from anmupB-containing strain) were unsuccessful. However, by cloning themupBgene into a shuttle vector, it was possible to transfer the resistance phenotype to susceptibleS. aureusby electroporation, proving thatmupBwas responsible for the high-level mupirocin resistance. Further studies need to be done to determine the prevalence ofmupBand to understand risk factors and outcomes associated with resistance mediated by this gene.