Research Article: Effects of the antimicrobial agent triclosan on the emergence of antibiotic resistance in Staphylococcus aureus

Abstract

In this study, we sought to determine if resistance to the antibacterial agent, triclosan, correlates with ciprofloxacin resistance in Staphylococcus aureus. To these ends, we isolated 8 mutant strains of S. aureus that were cross-resistant to both triclosan and ciprofloxacin when the drugs are present in bacterial media simultaneously. Surprisingly, the 8 mutant strains were as sensitive to triclosan as the wild type strain when grown in triclosan containing bacterial media lacking ciprofloxacin. This data suggests that triclosan resistance in these mutants is dependant on the presence of ciprofloxacin. These strains also displayed resistance to various concentrations of ethidium bromide. In other bacterial systems, resistance to ciprofloxacin and ethidium bromide is mediated by multi-drug efflux pumps. In order to evaluate the mechanism behind the triclosan/ciprofloxacin/ethidium bromide cross-resistance in our 8 mutant strains, we performed sequencing analyses on the promoter region of the S. aureus multi-drug efflux pump, NorA. NorA is the most well characterized drug efflux pump in S. aureus and is responsible for the efflux of both ciprofloxacin and ethidium bromide. The results from the sequencing analyses demonstrated that 3 of the 8 mutant strains displayed alterations in the NorA promoter region. Taken together, our results demonstrated that triclosan resistance can be correlated with ciprofloxacin resistance in S. aureus and that alterations in the NorA promoter may be responsible for the cross-resistant phenotypes of 3 of these mutant strains.