ONEILL AJ, COVE JH, CHOPRA I; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 130.

Univ. of Leeds, Leeds, United Kingdom

BACKGROUND: Fusidic acid (Fus) is a potent anti-staphylococcal agent that inhibits translation by targeting the prokaryotic ribosomal translocase, elongation factor G (EF-G). Although resistance alleles have been characterized in the EF-G gene (fusA) of Escherichia coli and Salmonella typhimurium (species for which the drug is not clinically useful), there are no reports on the molecular basis of fusidic acid-resistance (FusR) in S. aureus.METHODS: FusR mutants were selected by plating S. aureus 8325-4 onto agar containing Fus at 4x and 156x the MIC. Colonies were picked at random and Minimum Inhibitory Concentrations (MICs) determined. Mutants from all MIC class-marks underwent DNA sequencing of fusA.RESULTS: Selection at 4x Fus MIC gave rise to FusR mutants exhibiting MICs up to 32 microg/mL (500-fold increase in resistance). Higher level FusR mutants, displaying MICs up to 256 microg/mL (4000-fold increase over wild-type), were recovered by selection on 156x Fus MIC. Fus resistance resulted from point mutations in EF-G affecting one of 6 amino acid positions [table: see text].CONCLUSIONS: Fus resistance in S. aureus arises via point mutations in fusA. The mutations characterized are novel, since no equivalent amino acid substitutions at similar sites have been reported in E. coli and S. typhimurium. This suggests that mutations conferring Fus resistance may occur across a range of sites in prokaryotic EF-G. In S. aureus, residues 457 and 88 appear to be particularly important in the development of high-level Fus resistance.KEYWORDS: Elongation factor G; Fusidic acid; Staphylococcus aureus

Publication Types:

• Meeting Abstracts

Keywords:

• Amino Acid Substitution
• Base Sequence
• Escherichia coli
• Fusidic Acid
• Microbial Sensitivity Tests
• Mutation
• Peptide Elongation Factor G
• Point Mutation
• Salmonella typhimurium
• Staphylococcus aureus
• genetics

Other ID:

• GWAIDS0009403

UI: 102246901

From Meeting Abstracts