Candida albicans stimulates Streptococcus mutans microcolony development via cross-kingdom biofilm-derived metabolites

Abstract

Candida albicans is frequently detected with heavy infection of Streptococcus mutans in plaque-biofilms from children affected with early-childhood caries, a prevalent and costly oral disease. The presence of C. albicans enhances S. mutans growth within biofilms, yet the chemical interactions associated with bacterial accumulation remain unclear. Thus, this study was conducted to investigate how microbial products from this cross-kingdom association modulate S. mutans build-up in biofilms. Our data revealed that bacterial-fungal derived conditioned medium (BF-CM) significantly increased the growth of S. mutans and altered biofilm 3D-architecture in a dose-dependent manner, resulting in enlarged and densely packed bacterial cell-clusters (microcolonies). Intriguingly, BF-CM induced S. mutans gtfBC expression (responsible for Gtf exoenzymes production), enhancing Gtf activity essential for microcolony development. Using a recently developed nanoculture system, the data demonstrated simultaneous microcolony growth and gtfB activation in situ by BF-CM. Further metabolites/chromatographic analyses of BF-CM revealed elevated amounts of formate and the presence of Candida-derived farnesol, which is commonly known to exhibit antibacterial activity. Unexpectedly, at the levels detected (25–50 μM), farnesol enhanced S. mutans-biofilm cell growth, microcolony development, and Gtf activity akin to BF-CM bioactivity. Altogether, the data provide new insights on how extracellular microbial products from cross-kingdom interactions stimulate the accumulation of a bacterial pathogen within biofilms.

Antigen I/II mediates interactions between Streptococcus mutans and Candida albicans

“…Previous studies have reported that C. albicans promotes the growth of S. mutans in the two‐species biofilm, thus enhancing biofilm formation . In contrast, other studies have reported that C. albicans and S. mutans display no synergistic effect, and some reports even document that S. mutans inhibits growth and hyphal formation in C. albicans . Different results may be due to the use of different biofilm conditions.…”

“…8 In contrast, other studies have reported that C. albicans and S. mutans display no synergistic effect, and some reports even document that S. mutans inhibits growth and hyphal formation in C. albicans. [31][32][33][34] Different results may be due to the use of different biofilm conditions. In our model we observed that many C. albicans cells were in yeast or pseudohyphal form (Figure 2), which is consistent with previous studies that have shown that in low-pH environments C. albicans is typically found in yeast or pseudohyphal form rather than the hyphal form.…”

Fungi at the Scene of the Crime: Innocent Bystanders or Accomplices in Oral Infections?

“…This molecule is a key regulator of C. albicans biofilm formation [63], and has also been shown to augment antimicrobial therapy and decrease bacterial biofilm formation [64,65]. These effects are also observed with S. mutans, with high concentrations of the compound inhibiting biofilm formation [66,67]. Yet, interestingly, when at lower concentrations (25-50 μM) that are representative within these dualspecies biofilms, then it can stimulate S. mutans microcolony development and enhance biofilm formation [67].…”

“…These effects are also observed with S. mutans, with high concentrations of the compound inhibiting biofilm formation [66,67]. Yet, interestingly, when at lower concentrations (25-50 μM) that are representative within these dualspecies biofilms, then it can stimulate S. mutans microcolony development and enhance biofilm formation [67]. It is therefore thought that this is a key maintenance molecule with regard to regulating microbial fitness and biofilm formation in oral plaque [68].…”

Impact of farnesol and Corsodyl® on Candida albicans forming dual biofilm with Streptococcus mutans

“…This mixed biofilm is embedded in a matrix composed mainly of extracellular α-glucans generated by the activity of the glucosyltransferase B (GtfB) secreted by S. mutans. Mannans present on the outer cell wall of C. albicans mediate GtfB binding leading to the increased production of this matrix and modulation of interaction between bacteria and fungi within biofilm (Ellepola et al, 2017;Hwang et al, 2017;Kim et al, 2017). The cariogenic role of C. albicans is associated with acidogenicity and the fermentation of assimilated dietary sugars, resulting in the production of collagenolytic proteinases.…”