Abstract
The cross-kingdom interactions between Candida albicans and Actinomyces viscosus play critical roles in root caries. However, the key pathway by which C. albicans regulates its interactions with A. viscosus is unclear. Here, we first employed 39 volunteers with root caries and 37 caries-free volunteers, and found that the abundances of C. albicans and A. viscosus were significantly increased in the individuals with root caries and showed a strong positive correlation. Their dual-species combination synergistically promoted biofilm formation and root caries in rats. The arginine biosynthesis pathway of C. albicans was significantly upregulated in dual-species biofilms and dental plaques from another 10 root caries volunteers compared with the 10 caries-free volunteers. The exogenous addition of arginine increased the cariogenicity of the dual-species biofilm. The C. albicans ARG4, a key gene from the arginine biosynthesis pathway, null mutant failed to promote dual-species biofilm formation and root caries in rats; however, the addition of arginine restored its synergistic actions with A. viscosus. Our results identified the critical roles of the C. albicans arginine biosynthesis pathway in its cross-kingdom interactions with A. viscosus for the first time and indicated that targeting this pathway was a practical way to treat root caries caused by multiple species. IMPORTANCE Root caries is a critical problem that threatens the oral health of the elderly population. Our results identified the essential roles of the C. albicans arginine biosynthesis pathway in its cross-kingdom interactions with A. viscosus in root caries for the first time and indicated that targeting this pathway was a practical way to treat root caries caused by multiple species.