Streptococcus Mutans Membrane Vesicles Enhance Candida albicans Pathogenicity and Carbohydrate Metabolism

Abstract

<i>Streptococcus mutans</i> and <i>Candida albicans</i>, as the most common bacterium and fungus in the oral cavity respectively, are considered microbiological risk markers of early childhood caries. <i>S. mutans</i> membrane vesicles (MVs) contain virulence proteins, which play roles in biofilm formation and disease progression. Our previous research found that <i>S. mutans</i> MVs harboring glucosyltransferases augment <i>C. albicans</i> biofilm formation by increasing exopolysaccharide production, but the specific impact of <i>S. mutans</i> MVs on <i>C. albicans</i> virulence and pathogenicity is still unknown. In the present study, we developed <i>C. albicans</i> biofilms on the surface of cover glass, hydroxyapatite discs and bovine dentin specimens. The results showed that <i>C. albicans</i> can better adhere to the tooth surface with the effect of <i>S. mutans</i> MVs. Meanwhile, we employed <i>C. albicans</i> biofilm-bovine dentin model to evaluate the influence of <i>S. mutans</i> MVs on <i>C. albicans</i> biofilm cariogenicity. In the <i>S. mutans</i> MV-treated group, the bovine dentin surface hardness loss was significantly increased and the surface morphology showed more dentin tubule exposure and broken dentin tubules. Subsequently, integrative proteomic and metabolomic approaches were used to identify the differentially expressed proteins and metabolites of <i>C. albicans</i> when cocultured with <i>S. mutans</i> MVs. The combination of proteomics and metabolomics analysis indicated that significantly regulated proteins and metabolites were involved in amino acid and carbohydrate metabolism. In summary, the results of the present study proved that <i>S. mutans</i> MVs increase bovine dentin demineralization provoked by <i>C. albicans</i> biofilms and enhance the protein and metabolite expression of <i>C. albicans</i> related to carbohydrate metabolism.