Role of triclosan in stringent response induced antibiotic tolerance of Staphylococcus aureus.

The biocide triclosan is used extensively in both household and hospital settings. The chronic exposure to the biocide occurring in individuals that use triclosan-containing products results in low levels of triclosan present in the human body. Triclosan was proposed to induce antimicrobial resistance in bacteria (Suller & Russell, 2000). Antimicrobials have failed to control Staphylococcus aureus and often infection persist or relapse. Stringent response mediated by alarmones ppGpp and (p)ppGpp have been reported to induce various virulence pathways and might be involved in antibiotic resistance and tolerance (Salzer, 2023). Here we aim to analyse whether the fatty acid inhibitor triclosan impacts antibiotic tolerance in planktonic and biofilm grown S. aureus. We analysed different S. aureus strains and mutants deficient in (p)ppGpp synthesis. We show that physiological concentrations of triclosan protects S. aureus from bacterial killing by ciprofloxacin and vancomycin. Triclosan pretreatment also protected S. aureus biofilms against antibiotics as shown by live/dead cell staining and viable cell counting. In planktonic cultures the triclosan effect on antibiotic tolerance was independent of (p)ppGpp and there was no induction of the stringent response by triclosan treatment. However, in biofilms antibiotic tolerance was decreased in a pppGpp⁰ mutant. This suggests that the mode of action of triclosan varies in planktonic and biofilm. RNA-sequencing should unravel the molecular mechanism of triclosan induced tolerance.

Salzer, A., & Wolz, C. (2023). Role of (p) ppGpp in antibiotic resistance, tolerance, persistence and survival in Firmicutes. Microlife, 4, uqad009.

Suller, M., & Russell, A. (2000). Triclosan and antibiotic resistance in Staphylococcus aureus. Journal of Antimicrobial Chemotherapy, 46(1), 11-18.