Streptococcus mutansSecreted Products InhibitCandida albicansInduced Oral Candidiasis

In the oral cavity,Candidaspecies form mixed biofilms withStreptococcus mutans, a pathogenic bacterium that can secretequorum sensingmolecules with antifungal activity. In this study, we extracted and fractioned culture filtrate ofS. mutans, seeking antifungal agents capable of inhibiting the biofilms, filamentation, and candidiasis byCandida albicans. ActiveS. mutansUA159 supernatant filtrate components were extracted via liquid-liquid partition and fractionated on a C-18 silica column to resolveS. mutansfraction 1 (SM-F1) and fraction 2 (SM-F2). We found anti-biofilm activity for both SM-F1 and SM-F2 in a dose dependent manner and fungal growth was reduced by 2.59 and 5.98 log for SM-F1 and SM-F2, respectively. The SM-F1 and SM-F2 fractions were also capable of reducingC. albicansfilamentation, however statistically significant differences were only observed for the SM-F2 (p= 0.004). SM-F2 efficacy to inhibitC. albicanswas confirmed by its capacity to downregulate filamentation genesCPH1,EFG1,HWP1, andUME6. UsingGalleria mellonellaas an invertebrate infection model, therapeutic treatment with SM-F2 prolonged larvae survival. Examination of the antifungal capacity was extended to a murine model of oral candidiasis that exhibited a reduction inC. albicanscolonization (CFU/mL) in the oral cavity when treated with SM-F1 (2.46 log) and SM-F2 (2.34 log) compared to the control (3.25 log). Although both SM-F1 and SM-F2 fractions decreased candidiasis in mice, only SM-F2 exhibited significant quantitative differences compared to the non-treated group for macroscopic lesions, hyphae invasion, tissue lesions, and inflammatory infiltrate. Taken together, these results indicate that the SM-F2 fraction contains antifungal components, providing a promising resource in the discovery of new inhibitors for oral candidiasis.