V-ATPase contributes to the cariogenicity of Candida albicans- Streptococcus mutans biofilm

The interaction between Candida albicans and Streptococcus mutans plays an important role in the progression of dental caries. The vacuolar proton pump (V-ATPase) is a vital enzyme regulating the growth and virulence of C. albicans, which is a potential target for caries prevention. However, the effect of V-ATPase on the cariogenicity of C. albicans-S. mutans biofilm remains to be explored. In this study, the detection rate of C. albicans in caries-active (group CA) (22.03%) was significantly higher than that in caries-free (group CF) children (8.00%), and the expression of V-ATPase related genes were higher in group CA. Then, the higher expressed V-ATPase coding genes VMA3, VMA4 and VMA11 in CA group were knocked out. Compared with the wild type SC5314, the mutants showed slower growth rate, inhibited hyphal growth, and defective integrity of cell wall. The biofilm biomass and extracellular polysaccharide (EPS) production of dual biofilm were significantly reduced, and the biofilm structure was impacted. Transcriptome analysis indicated that V-ATPase participated in various metabolisms and biosynthesis pathways of C. albicans, and influenced EPS metabolism of S. mutans. Finally, compared with the positive control, the caries severity, the biomass and EPS production of dental plaque were significantly reduced after deletion of VMA3, VMA4 and VMA11 in vivo. This study revealed for the first time the regulating effect of V-ATPase on the cariogenicity of C. albicans-S. mutans biofilm and its potential mechanisms. The results may provide basis for new strategies of ecological prevention and treatment of dental caries.