AUTHOR=dos Santos Jéssica Diane , Fugisaki Luciana Ruano de Oliveira , Medina Rebeca Previate , Scorzoni Liliana , Alves Mariana de Sá , de Barros Patrícia Pimentel , Ribeiro Felipe Camargo , Fuchs Beth Burgwyn , Mylonakis Eleftherios , Silva Dulce Helena Siqueira , Junqueira Juliana Campos 

TITLE=Streptococcus mutans Secreted Products Inhibit Candida albicans Induced Oral Candidiasis

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.01605

DOI=10.3389/fmicb.2020.01605

ISSN=1664-302X

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