AUTHOR=van de Lagemaat Marieke , Stockbroekx Valerie , Geertsema-Doornbusch Gésinda I. , Dijk Melissa , Carniello Vera , Woudstra Willem , van der Mei Henny C. , Busscher Henk J. , Ren Yijin 

TITLE=A Comparison of the Adaptive Response of Staphylococcus aureus vs. Streptococcus mutans and the Development of Chlorhexidine Resistance

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.861890

DOI=10.3389/fmicb.2022.861890

ISSN=1664-302X

ABSTRACT=Antimicrobials with non-selective antibacterial efficacy, such as chlorhexidine can be effective in reducing biofilm, but bear the risk of inducing resistance in specific strains. Clinically, strains such as Staphylococcus aureus have been found resistant to chlorhexidine, but other strains, including Streptococcus mutans have largely remained susceptible to chlorhexidine despite its wide-spread use in oral health care. Here we aim to forward a possible reason as to why S. aureus can acquire resistance against chlorhexidine, while S. mutans remains susceptible. Measurement of surface enhanced fluorescence indicated that chlorhexidine caused gradual but irreversible deformation to adhering, green-fluorescent S. aureus due irreparable damage to the cell wall. Concurrently, the metabolic activity of adhering staphylococci was high, suggesting efflux mechanisms may have been activated upon cell wall deformation, impeding the build-up of a high chlorhexidine concentration in the cytoplasm and therewith stimulating the development of chlorhexidine-resistance in S. aureus. Exposure of S. mutans to chlorhexidine caused immediate but reversible deformation in adhering streptococci, indicative of rapid self-repair of cell wall damage done by chlorhexidine. Due to cell wall self-repair, S. mutans will be unable to effectively reduce the chlorhexidine concentration in the cytoplasm causing solidification of the cytoplasm. In line, no increased metabolic activity was observed in S. mutans during exposure to chlorhexidine. Therewith, self-repair is suicidal and prevents the development of a chlorhexidine-resistant progeny in S. mutans.