Multidisciplinary research agenda for novel antimicrobial agents for caries prevention and treatment.

Antimicrobial methods to augment fluoride-mediated caries inhibition are necessary. Several methods are described here, but none was considered likely to be as effective as fluoride usage. None had been tested in effective models to demonstrate their ability to act either additively or synergistically with fluoride-containing toothpastes. Dental caries is a biofilm-mediated disease: The composition of the biofilm associated with caries initiation and progression is diverse. Caries-associated taxa - including mutans streptococci, lactobacilli, bifidobacteria, and yeasts - may be useful surrogate markers for in vivo investigations. In vitro testing should progress from single-species planktonic cells to multi-species biofilms prior to essential testing in randomized control trials (RCTs). Modern high-throughput sequencing techniques need to be applied to the study of bacterial acquisition from birth and of the composition of the biofilm associated with the formation of white-spot lesions. The determination of the functions of the biofilm and the phenotype of the bacterial components may be determined by RNA-seq techniques, since they must be conserved between caries lesions and will include the ability to produce acids and survive and proliferate in acidic conditions. The application of such methods will significantly improve our understanding of the etiology and progression of dental caries.