Candida albicans CHK1 gene regulates its cross-kingdom interactions with Streptococcus mutans to promote caries.

Abstract

The cross-kingdom interactions between Candida albicans and Streptococcus mutans have played important roles in early childhood caries (ECC). However, the key pathways of C. albicans promoting the cariogenicity of S. mutans are still unclear. Here, we found that C. albicans CHK1 gene was highly upregulated in their dual-species biofilms. C. albicans chk1Δ/Δ significantly reduced the synergistical growth promotion, biofilm formation, and exopolysaccharides (EPS) production of S. mutans, the key cariogenic agent, compared to C. albicans wild type (WT) and CHK1 complementary strains. C. albicans WT upregulated the expressions of S. mutans EPS biosynthesis genes gtfB, gtfC, and gtfD, and their regulatory genes vicR and vicK, but chk1Δ/Δ had no effects. Both C. albicans WT and chk1Δ/Δ failed to promote the biofilm formation and EPS production of S. mutans ΔvicK and antisense-vicR strains, indicating that C. albicans CHK1 upregulated S. mutans vicR and vicK to increase the EPS biosynthesis gene expression, then enhanced the EPS production and biofilm formation to promote the cariogenicity. In rat caries model, the coinfection with chk1Δ/Δ and S. mutans decreased the colonization of S. mutans and developed less caries especially the severe caries compared to that from the combinations of S. mutans with C. albicans WT, indicating the essential role of C. albicans CHK1 gene in the development of dental caries. Our study for the first time demonstrated the key roles of C. albicans CHK1 gene in dental caries and suggested that it may be a practical target to reduce or treat ECC. KEY POINTS: • C. albicans CHK1 gene is important for its interaction with S. mutans. • CHK1 regulates S. mutans two-component system to promote its cariogenicity. • CHK1 gene regulates the cariogenicity of S. mutans in rat dental caries.