Salicylate-inducible multiple antimicrobial resistance in Staphylococcus aureus.

摘要

The primary in vivo metabolite of aspirin, salicylate, is a natural biochemical that has toxic effects on tissues and cell growth, acts as a signaling molecule for the induction of plant defenses, and modulates antimicrobial susceptibility in bacteria. Aspirin is used therapeutically for the treatment of inflammation, and for the prophylactic chemoprevention of cancer and heart disease. Salicylate toxicity results from the inhibition of cyclooxygenases, energy metabolism down-regulation and alterations in membrane permeability.;Salicylate-inducible antimicrobial resistance results from the specific transcriptional modulation of antimicrobial resistance genes and nonspecific physiochemical effects on membrane permeability. In Escherichia coli and other Gram negative genera, salicylate stimulates expression of the multiple antibiotic resistance mar operon, leading to the up-regulation of antimicrobial efflux and a decrease in permeability through down-regulation of porin synthesis.;In the Gram positive nosocomial pathogen Staphylococcus aureus , full expression of salicylate-inducible resistance is dependent on the transcriptional modulation of global regulators such as the alternative sigma factor (sigB), and the staphylococcal accessory regulator (sarA). De-repression of drug efflux pumps via salicylate-inducible down-regulation of the major gene regulator (mgrA) also contributes to phenotypic resistance to antimicrobials. In both E. coli and S. aureus, salicylate also stimulates antimicrobial resistance by the induction of a passive membrane permeability barrier.;In S. aureus, salicylate reduces flux through glycolysis, which likely contributes to growth inhibition. As slow-growing bacteria express increased resistance to antimicrobials, a reduction in glycolysis in salicylate-induced populations may be associated with increased phenotypic resistance to multiple antimicrobials. The effects of aspirin and salicylate on disease, virulence and drug resistance are not fully understood.