Abstract
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.
Highlights
We observed reductions in the CFU/mL number of C. albicans for the biofilms treated with SMF1 and SM-F2 in all tested concentrations when compared to the non-treated control group
In the group treated with 15 mg/mL SM-F2 (n = 5), three biofilms showed a total inhibition of C. albicans cells (Figure 1)
S. mutans fraction 1 (SM-F1) and SM-F2 exhibited anti-biofilm activity against C. albicans in a dose dependent manner, with SMF2 being the most effective inhibitory fraction
Summary
Oral candidiasis is the most common opportunistic fungal infection of the oral cavity and represents a significant clinical problem, especially in elderly denture wearers, HIV-infected individuals, and patients undergoing antineoplastic therapy (Coronado-Castellote and JimenezSoriano, 2013; Garcia-Cuesta et al, 2014; Seneviratne and Rosa, 2016; Zhang et al, 2016; Antifungal Activity of Streptococcus mutans on Candida albicansVenkatasalu et al, 2020). Oral candidiasis is the most common opportunistic fungal infection of the oral cavity and represents a significant clinical problem, especially in elderly denture wearers, HIV-infected individuals, and patients undergoing antineoplastic therapy The manifestations of oral candidiasis can occur in the lips, skin, and mucosa and have different clinical and histopathological variants (Coronado-Castellote and Jimenez-Soriano, 2013; Costa et al, 2013b; Zhang et al, 2016). The pathogenicity of C. albicans involves a significant co-regulation between adherence, biofilm formation, and hyphal development (Breger et al, 2007)
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