Dataset Information

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.

SUBMITTER: Yang JA

PROVIDER: S-EPMC2721991 | biostudies-literature | 2006 Oct

REPOSITORIES: biostudies-literature

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Molecular analysis of isoleucyl-tRNA synthetase mutations in clinical isolates of methicillin-resistant Staphylococcus aureus with low-level mupirocin resistance.

Yang Jin Ah JA Park Dae Won DW Sohn Jang Wook JW Yang In Seok IS Kim Kyung Hyun KH Kim Min Ja MJ

Journal of Korean medical science 20061001 5

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 ...[more]

PMID: 17043414

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Project description:Mupirocin, a topical antimicrobial agent, is an important component in the eradication of methicillin-resistant Staphylococcus aureus (MRSA) colonization. The molecular characteristics of 46 mupirocin-resistant MRSA (MR-MRSA) clinical isolates were analyzed by multilocus sequence typing (MLST), staphylococcal cassette chromosome mec element (SCCmec) typing, spa typing, and analysis of virulence genes. All 26 MRSA isolates with low-level mupirocin resistance possessed a V588F mutation in ileS. Among 20 MRSA isolates with high-level resistance to mupirocin, all carried mupA; 2 isolates also possessed the V588F mutation in ileS, and 1 possessed the V631F mutation in ileS (isoleucyl-tRNA synthetase). The majority of MR-MRSA isolates were resistant to erythromycin, clindamycin, tetracycline, ciprofloxacin, and gentamicin, but the rates of resistance to rifampin and fusidic acid were 8.7% and 6.5%, respectively. Eight sequence types (STs) were found among the 46 MR-MRSA isolates, of which ST764 was the most prevalent (76.1%). The most frequent spa type identified was t1084 (52.2%). The SCCmec type most frequently found was type II (80.4%). The most common clone among low-level MR-MRSA isolates was ST764-MRSA-SCCmec type II-t1084 (23 isolates), while ST764-MRSA-SCCmec type II-t002 (9 isolates) was the most common clone among high-level MR-MRSA isolates. Additionally, all toxin genes except the seb gene were not identified among ST764 isolates. Among clonal complex 5 (CC5) isolates, immune evasion cluster (IEC)-associated genes (chp, sak, and scn) and seb were present in ST764 but absent in ST5, while sec, sel1, tsst-1, and hlb genes were identified in ST5 but absent in ST764. In conclusion, the spread of CC5 clones, especially a novel ST764-MRSA-SCCmec type II-t1084 clone with high-level resistance to mupirocin, was responsible for the increase in mupirocin resistance. These findings indicated that the emergence of the ST764 MR-MRSA clone involves a therapeutic challenge for treating serious MRSA infections. IMPORTANCE Mupirocin, a topical antibiotic that is commonly used for the nasal decolonization of MRSA and methicillin-sensitive Staphylococcus aureus in hospital settings and nursing homes, was introduced as a highly effective antibiotic against MRSA. Mupirocin acts by competitively binding isoleucyl-tRNA synthetase, thereby disrupting protein synthesis. This drug shows bacteriostatic and bactericidal activity at low and high concentrations, respectively. However, with the increase in mupirocin use, low-level and high-level resistance during nasal mupirocin treatment has been reported. In a previous study, the proportion of MRSA strains with high-level mupirocin resistance in a Canadian hospital increased from 1.6% in the first 5 years of surveillance (1995 to 1999) to 7.0% (2000 to 2004).

Dataset Information

Molecular analysis of isoleucyl-tRNA synthetase mutations in clinical isolates of methicillin-resistant Staphylococcus aureus with low-level mupirocin resistance.

Publications

Molecular analysis of isoleucyl-tRNA synthetase mutations in clinical isolates of methicillin-resistant Staphylococcus aureus with low-level mupirocin resistance.

Similar Datasets

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