Human Tooth as a Fungal Niche: Candida albicans Traits in Dental Plaque Isolates

Candida albicans, a fungus typically found in the mucosal niche, is frequently detected in biofilms formed on teeth (dental plaque) of toddlers with severe childhood caries, a global public health problem that causes rampant tooth decay. However, knowledge about fungal traits on the tooth surface remains limited. Here, we assess the phylogeny, phenotype, and interkingdom interactions of C. albicans isolated from plaque of diseased toddlers and compare their properties to reference strains, including 529L (mucosal isolate). C. albicans isolates exhibit broad phenotypic variations, but all display cariogenic traits, including high proteinase activity, acidogenicity, and acid tolerance. Unexpectedly, we find distinctive variations in filamentous growth, ranging from hyphal defective to hyperfilamentous. We then investigate the ability of tooth isolates to form interkingdom biofilms with Streptococcus mutans (cariogenic partner) and Streptococcus gordonii (mucosal partner). The hyphal-defective isolate lacks cobinding with S. gordonii, but all C. albicans isolates develop robust biofilms with S. mutans irrespective of their filamentation state. Moreover, either type of C. albicans (hyphae defective or hyperfilamentous) enhances sucrose metabolism and biofilm acidogenicity, creating highly acidic environmental pH (<5.5). Notably, C. albicans isolates show altered transcriptomes associated with pH, adhesion, and cell wall composition (versus reference strains), further supporting niche-associated traits. Our data reveal that C. albicans displays distinctive adaptive mechanisms on the tooth surface and develops interactions with pathogenic bacteria while creating an acidogenic state regardless of fungal morphology, contrasting with interkingdom partnerships in mucosal infections. Human tooth may provide new insights into fungal colonization/adaptation, interkingdom biofilms, and contributions to disease pathogenesis. IMPORTANCE Severe early childhood caries is a widespread global public health problem causing extensive tooth decay and systemic complications. Candida albicans, a fungus typically found in mucosal surfaces, is frequently detected in dental plaque formed on teeth of diseased toddlers. However, the clinical traits of C. albicans isolated from tooth remain underexplored. Here, we find that C. albicans tooth isolates exhibit unique biological and transcriptomic traits. Notably, interkingdom biofilms with S. mutans can be formed irrespective of their filamentation state. Furthermore, tooth isolates commonly share dental caries-promoting functions, including acidogenesis, proteolytic activity, and enhanced sugar metabolism, while displaying increased expression of pH-responsive and adhesion genes. Our findings reveal that C. albicans colonizing human teeth displays distinctive adaptive mechanisms to mediate interkingdom interactions associated with a disease-causing state on a mineralized surface, providing new insights into Candida pathobiology and its role in a costly pediatric disease.