title: Molecular analysis of isoleucyl-tRNA synthetase mutations in clinical isolates of methicillin-resistant Staphylococcus aureus with low-level mupirocin resistance.
abstract: Emergence and spread of low-level mupirocin resistance in staphylococci have been increasingly reported in recent years. The aim of this study was to characterize missense mutations within the chromosomal isoleucyl-tRNA synthetase gene (ileS) among clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) with low-level mupirocin resistance. A total of 20 isolates of MRSA with low-level mupirocin resistance (minimal inhibitory concentration, 16-64 microg/mL) were collected from 79 patients in intensive care units for six months. The isolates were analyzed for isoleucyl-tRNA synthetase (IleS) mutations that might affect the binding of mupirocin to the three-dimensional structure of the S. aureus IleS enzyme. All isolates with low-level mupirocin resistance contained the known V588F mutation affecting the Rossman fold, and some of them additionally had previously unidentified mutations such as P187F, K226T, F227L, Q612H, or V767D. Interestingly, Q612H was a novel mutation that was involved in stabilizing the conformation of the catalytic loop containing the KMSKS motif. In conclusion, this study confirms that molecular heterogeneity in ileS gene is common among clinical MRSA isolates with low-level mupirocin resistance, and further study on clinical mutants is needed to understand the structural basis of low-level mupirocin resistance.
authors.affiliation: Research Institute of Emerging Infectious Diseases, Korea University, Seoul, Korea.
authors.forename: Jin Ah
authors.initials: JA
authors.lastname: Yang
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Park
authors.forename: Jang Wook
authors.initials: JW
authors.lastname: Sohn
authors.forename: In Seok
authors.initials: IS
authors.lastname: Yang
authors.forename: Kyung Hyun
authors.initials: KH
authors.lastname: Kim
authors.forename: Min Ja
authors.initials: MJ
authors.lastname: Kim
mesh_terms: D024881:Drug Resistance, Bacterial; D016521:Electrophoresis, Gel, Pulsed-Field; D006801:Humans; D007362:Intensive Care Units; D007533:Isoleucine-tRNA Ligase / Q000235:genetics*; D016106:Methicillin Resistance; D016712:Mupirocin / Q000494:pharmacology*; D020125:Mutation, Missense; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics*
chemical_list: D016712:Mupirocin; D007533:Isoleucine-tRNA Ligase