Streptococcus mutans Secreted Products Inhibit Candida albicans Induced Oral Candidiasis

• Published in: Frontiers in microbiology Vol. 11; p. 1605
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 15-07-2020
• Subjects: biofilm; Candida albicans; filamentation; Microbiology; oral candidiasis; Streptococcus mutans
• ISSN: 1664-302X; 1664-302X
• DOI: 10.3389/fmicb.2020.01605

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.