title: MupB, a new high-level mupirocin resistance mechanism in Staphylococcus aureus.
abstract: Mupirocin is a topical antibiotic used for the treatment of skin infections and the eradication of methicillin-resistant Staphylococcus aureus carriage. 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 of mupA (ileS2), which encodes an alternate isoleucyl-tRNA synthetase. In this study, we describe high-level mupirocin resistance mediated by a novel locus, mupB. The mupB gene (3,102 bp) shares 65.5% sequence identity with mupA but only 45.5% identity with ileS. 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 an mupB-containing strain) were unsuccessful. However, by cloning the mupB gene into a shuttle vector, it was possible to transfer the resistance phenotype to susceptible S. aureus by electroporation, proving that mupB was responsible for the high-level mupirocin resistance. Further studies need to be done to determine the prevalence of mupB and to understand risk factors and outcomes associated with resistance mediated by this gene.
authors.affiliation: Ontario Agency for Health Protection and Promotion, Public Health Laboratory, Toronto, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Seah
authors.forename: David C
authors.initials: DC
authors.lastname: Alexander
authors.forename: Lisa
authors.initials: L
authors.lastname: Louie
authors.forename: Andrew
authors.initials: A
authors.lastname: Simor
authors.forename: Donald E
authors.initials: DE
authors.lastname: Low
authors.forename: Jean
authors.initials: J
authors.lastname: Longtin
authors.forename: Roberto G
authors.initials: RG
authors.lastname: Melano
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D003001:Cloning, Molecular; D003227:Conjugation, Genetic; D004269:DNA, Bacterial / Q000096:biosynthesis / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D016521:Electrophoresis, Gel, Pulsed-Field; D018274:Electroporation; D016680:Genome, Bacterial / Q000235:genetics; D007533:Isoleucine-tRNA Ligase / Q000096:biosynthesis / Q000235:genetics; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000235:genetics; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D016712:Mupirocin / Q000494:pharmacology*; D020125:Mutation, Missense / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D016133:Polymerase Chain Reaction; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics*; D014169:Transformation, Bacterial
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; C573018:MupB protein, Staphylococcus aureus; D016712:Mupirocin; D007533:Isoleucine-tRNA Ligase