Candida albicans Colonization Promotes Root Caries by Enhancing Cariogenicity of Oral Biofilm

Objectives: To investigate the role of Candida albicans in the pathogenesis of root caries, and to identify potential factor that determines the caries-promoting effect of this fungal species.
Methods: The detection rate and abundance of C. albicans, as well as the Streptococcus mutans/Streptococcus sanguinis ratio in the root caries lesion were determined, and linear regression was performed using the concentration of C. albicans and ratio of S. mutans/S. sanguinis. The S. mutans/S. sanguinis ratio when co-cultured with C. albicans was further quantified by both qPCR and FISH . The cariogenicity of the 3-species biofilm was further evaluated with both in vitro demineralization model and rat root caries model. The pH-responsive genes of C. albicans was further screened to identify the major factor that mainly determines the cariogenicity-promoting effect of this fungal species.
Results: We observed significantly increased colonization of C. albicans in supragingival dental plaque of root-caries subjects compared to caries-free controls. C. albicans colonization altered the microbial composition of oral biofilm, particularly increased the ratio of S. mutans/S. sanguinis. More importantly, C. albicans colonization increased the cariogenicity of oral biofilm, specifically by enhancing the acid production and demineralization activity of saliva-derived biofilms. The cariogenicity-modulating activity of C. albicans on oral biofilm was dependent on PHR2 under cariogenic conditions. phr2Δ/Δ showed decreased colonization and cariogenicity-modulating activity on either in vitro artificial caries model or in vivo root caries rat model.
Conclusions: Our data indicate the critical role of C. albicans infection in the occurrence of root caries. C. albicans increases the cariogenicity of oral biofilm by modulating the microbial composition of aciduric and alkali-generating oral streptococci. PHR2 is the major factor that determines the successful colonization of C. albicans in a mixed microbial consortium under cariogenic conditions.