Molecules Targeting EriC^F1 Increase Streptococcus mutans Fluoride Sensitivity.

Area of Science:

• Microbiology
• Biochemistry
• Dental Research

Background:

• Dental caries is a major global oral health issue.
• Fluoride prevents caries but is insufficient against Streptococcus mutans.
• Streptococcus mutans has a fluoride detoxification mechanism involving exporters.

Purpose of the Study:

• Identify the functional fluoride exporter in Streptococcus mutans.
• Develop novel compounds to enhance fluoride's antibacterial efficacy.
• Investigate new therapeutic strategies for dental caries prevention.

Main Methods:

• Constructed gene deletion, overexpression, and complemented strains of S. mutans UA159.
• Assessed fluoride sensitivity, intracellular fluoride levels, and cell membrane permeability.
• Used molecular docking to identify diphenylurea derivatives targeting the fluoride exporter.
• Performed chequerboard broth microdilution assays and in vivo studies.

Main Results:

• EriC^F1 identified as the major functional fluoride exporter in S. mutans.
• Three diphenylurea derivatives synergistically enhanced sodium fluoride's antibacterial effect by impeding fluoride efflux.
• Compounds 9 and 15 combined with sodium fluoride significantly reduced S. mutans cariogenicity in vivo with good biocompatibility.

Conclusions:

• Fluoride exporters in S. mutans are potential targets for caries prevention.
• Diphenylurea derivatives targeting EriC^F1 offer a promising therapeutic approach when combined with fluoride.
• This strategy provides novel measures for effective dental caries prevention.