Effects of salicylate and related compounds on fusidic acid MICs in Staphylococcus aureus

• Published in: Journal of antimicrobial chemotherapy 1999-07, Vol.44 (1), p.57-64
• Main Authors: PRICE, C. T. D, O'BRIEN, F. G, SHELTON, B. P, WARMINGTON, J. R, GRUBB, W. B, GUSTAFSON, J. E
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Aspirin - pharmacology; Bacteriology; Bacteriophage Typing; Benzoates - pharmacology; Biological and medical sciences; DNA, Bacterial - genetics; Drug Resistance, Microbial - genetics; Electrophoresis, Gel, Pulsed-Field; Fundamental and applied biological sciences. Psychology; Fusidic Acid - pharmacology; Humans; Ibuprofen - pharmacology; Medical sciences; Microbial Sensitivity Tests; Microbiology; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Pharmacology. Drug treatments; Salicylates - pharmacology; Staphylococcus aureus; Staphylococcus aureus - classification; Staphylococcus aureus - drug effects; Staphylococcus aureus - growth & development
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/44.1.57

Salicylate, acetyl-salicylate, benzoate and ibuprofen increased fusidic acid MICs for fusidic acid-resistant and -susceptible strains of Staphylococcus aureus representing six genetic lineages. The effects of these substances on fusidic acid resistance levels occurred in a strain-dependent manner. The weak acid acetate, and acetaminophen did not alter fusidic acid resistance levels, while the addition of saligenin, the alcohol of salicylate, reduced gradient plate MICs for all strains studied. These findings indicate that a benzoic acid structure is required for the induction of increased intrinsic fusidic acid resistance levels. When 2 mM salicylate was added to media used in population analyses, the number of cells able to survive on high concentrations of fusidic acid increased. This increase in cell survival was observed in two unrelated fusidic acid-resistant strains, with chromosomal (WBG8287) or plasmid (WBG1576) mediated resistance determinants and two unrelated susceptible strains. The salicylate-induced increase in fusidic acid resistance was phenotypic at low fusidic acid concentrations (relative to resistance phenotype) for WBG8287 and a fusidic acid-susceptible strain. On media containing salicylate and high fusidic acid concentrations, the mutation frequency to higher fusidic acid resistance levels was greater for WBG8287, compared with unsupplemented fusidic acid-containing media. These experiments provide evidence for a novel salicylate inducible fusidic acid resistance mechanism in S. aureus.