Antibacterial and cytotoxic effects of chlorhexidine combined with sodium DNA on oral microorganisms: an in vitro study usingDictyostelium discoideum

Background: Chlorhexidine (CHX) is widely used in oral care for its broad-spectrum antimicrobial activity but can cause significant side effects. Sodium DNA has emerged as a potential adjunct capable of modulating cellular responses. Aim: This study assessed whether sodium DNA enhances the antibacterial and antibiofilm activity of 0.20% and 0.12% CHX mouthwashes against Streptococcus mutans and Escherichia coli, and evaluated their effects on the viability and phagocytic activity of Dictyostelium discoideum, a model for mammalian phagocytes. Results: All CHX-containing mouthwashes were bactericidal against S.mutans, regardless of sodium DNA, whereas CHX-only formulations were more effective against E.coli in time–kill assays. All formulations inhibited biofilm formation at 50–0.01%. In S. mutans, early biofilms were strongly inhibited (50–0.39%), whereas mature biofilms were less affected. In E. coli, sodium DNA enhanced inhibition of both biofilm formation (50–1.56%) and mature biofilms (50–3.12%). The 0.12% CHX–sodium DNA formulation most effectively modulated D.discoideum viability and phagocytic activity, and metabolomics showed that sodium DNA reduced CHX-induced metabolic stress. Conclusions: This study integrates antimicrobial, antibiofilm, cellular, and metabolomic analyses to assess CHX with sodium DNA. Sodium DNA reduces CHX-induced cytotoxicity and metabolic stress while maintaining antimicrobial activity, offering insights for optimizing oral hygiene formulations through combined microbial and host-cell evaluation.