Streptococcus mutans Secreted Products Inhibit Candida albicans Induced Oral Candidiasis.

In the oral cavity, Candida species form mixed biofilms with Streptococcus mutans, a pathogenic bacterium that can secrete quorum sensing molecules with antifungal activity. In this study, we extracted and fractioned culture filtrate of S. mutans, seeking antifungal agents capable of inhibiting the biofilms, filamentation, and candidiasis by Candida albicans. Active S. mutans UA159 supernatant filtrate components were extracted via liquid-liquid partition and fractionated on a C-18 silica column to resolve S. mutans fraction 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 reducing C. albicans filamentation, however statistically significant differences were only observed for the SM-F2 (p = 0.004). SM-F2 efficacy to inhibit C. albicans was confirmed by its capacity to downregulate filamentation genes CPH1, EFG1, HWP1, and UME6. Using Galleria mellonella as 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 in C. albicans colonization (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.

Effects of surface pre-reacted glass-ionomer (S-PRG) eluate on Candida spp.: antifungal activity, anti-biofilm properties, and protective effects on Galleria mellonella against C. albicans infection.

Surface pre-reacted glass-ionomer (S-PRG) is a bioactive filler produced by PRG technology, which is applied to various dental materials. The inhibitory effects of S-PRG eluate against Candida, the most common fungal oral pathogen, were investigated. Minimum inhibitory concentrations (MIC) and anti-biofilm activities were tested against Candida albicans, Candida glabrata, Candida krusei, and Candida tropicalis. For the in vivo study, Galleria mellonella was used as a model to evaluate the effects of S-PRG on toxicity, hemocyte counts and candidiasis. The MIC of S-PRG ranged from 5 to 40% (v/v). S-PRG eluate exhibited anti-biofilm activity for all the Candida species tested. Furthermore, injection of S-PRG eluate into G. mellonella was not toxic to the larvae and protected G. mellonella against experimental candidiasis. In addition, S-PRG eluate inhibited biofilm formation by C. albicans, C. glabrata, C. krusei, and C. tropicalis and exerted protective effects on G. mellonella against experimental candidiasis in vivo.

Influence of Candida krusei and Candida glabrata on Candida albicans gene expression in in vitro biofilms.

OBJECTIVE: The present study aimed to evaluate the interactions between the species Candida albicans, Candida krusei and Candida glabrata in monotypic and mixed biofilm models formed in vitro as well as the relative expression of the ALS1, ALS3, HWP1, BCR1, EFG1, TEC1, SAP5, PLB2 and LIP9 genes. MATERIAL AND METHODS: Mixed (C. albicans/C. krusei and C. albicans/C. glabrata) and monotypic biofilms were cultured for 0, 12 and 24h. Gene expression was analyzed in the same biofilm model in which the number of CFU/mL was counted. RESULTS: The C. albicans CFU/mL values were lower at the 12 and 24h time points in the mixed biofilms compared with the monotypic biofilms, and decreases of 56.23% and 64.4% in C. albicans were observed when this species was associated with C. glabrata and C. krusei, respectively. In the presence of C. krusei, the expression of the ALS3, HWP1, BCR1, EFG1 and TEC1 genes of C. albicans was completely inhibited, indicating both transcriptome and the phenotypic antagonism between these two species, but genes related to the secretion of enzymes were stimulated. In the presence of C. glabrata, C. albicans showed a similar gene expression profile to that obtained in association with C. krusei, though it was altered to a lesser degree. CONCLUSION: We conclude that C. krusei and C. glabrata may alter or inhibit the mechanisms involved in the in vitro adherence and formation of C. albicans biofilms, influencing the pathogenicity of this species and suggesting a competitive interaction with C. krusei and C. glabrata in biofilm formation.