The dlt operon contributes to the resistance to chlorhexidine in Streptococcus mutans

Chlorhexidine (CHX) is considered to be the gold standard for dental caries prevention and is widely applied in dental practice. However, the long-term application of CHX may result in CHX-resistance in oral pathogens. The aim of this study was to investigate whether long-term use of CHX causes resistance in Streptococcus mutans and to explore the possible associated mechanisms. Four different S. mutans strains were chosen for this study to exclude the specificity of strains. The four strains displayed an increase in minimum inhibitory concentration (MIC) after exposure to CHX for 10 passages. The features and cariogenicity of S. mutans CHX-resistant strains (SM-Cs) that were exposed to CHX for 10 passages with increased MIC did not differ significantly to the parental strains. The SM-Cs were more hydrophobic than the parental strains. The dltC and dltD genes were upregulated in SM-Cs. Relative expression of the BceA, BceR, and SMU.862 genes in SM-Cs was similar to or lower than that of the parental strains. The MIC value was significantly lower in dltC knockout mutants. These findings confirmed that continuous exposure to CHX could induce CHX-resistance in S. mutans. The increased cell surface hydrophobicity and upregulated expression of dlt operon were possible underlying mechanisms of CHX-resistance in S. mutans.