oralpresentation
Description

Title: 1167 - Streptococcus mutans-derived Exopolysaccharides Enhance Antifungal Tolerance in Cross-kingdom Oral Biofilms

Authors:

Dongyeop Kim (Presenter)
University of Pennsylvania

Yuan Liu, University of Pennsylvania
Yong Li, University of Pennsylvania
Áurea Simon-Soro, University of Pennsylvania
Geelsu Hwang, University of Pennsylvania
Hyun (Michel) Koo, University of Pennsylvania

Abstract:

Objectives: Candida albicans is frequently detected with Streptococcus mutans in plaque-biofilms from toddlers affected with early-childhood caries (ECC). The presence of C. albicans enhances α-glucans synthesis by S. mutans glucosyltransferases (Gtfs), enmeshing the microorganisms in an exopolysaccharides (EPS) matrix and promoting the accumulation of pathogenic mixed-kingdom biofilms. Here, we investigated whether topical treatment of clinically used antifungal (fluconazole) and antimicrobial (povidone iodine) agents can disrupt bacterial-fungal association.

Methods: Drug efficacy was determined using in vitro and in vivo biofilm models via biochemical/microbiological techniques (carbohydrate and microbiome analyses) combined with high-resolution confocal microscopy. Drug interaction with S. mutans GtfB-derived glucans was examined by real-time live-cell imaging and scintillation spectroscopy, while drug susceptibility was assessed using gtfB-defective bacterial strain in mixed-kingdom biofilm and EPS-digesting glucanohydrolases.

Results: We observed that fluconazole and povidone iodine alone had only moderate antifungal and antibacterial activity against biofilms on teeth. However, we unexpectedly found that the combination of agents completely eradicated C. albicans viable population and disrupted mixed biofilm formation in vivo, while shifting the plaque bacteriome composition. Notably, the addition of povidone iodine enhanced the killing efficacy of fluconazole against C. albicans by potently reducing the activity of GtfB and glucan synthesis in situ, and thereby disrupting the assembly of the protective EPS-matrix. Mechanistically, we found that GtfB-derived EPS produced on C. albicans surface can directly bind and sequester fluconazole, thereby reducing the uptake of the agent into the fungal cell. Conversely, inhibition/enzymatic degradation of the α-glucan matrix or co-culturing with gtfB-defective S. mutans re-established the antifungal susceptibility of C. albicans within biofilms.

Conclusions: The data provide new insights for treatment of a virulent cross-kingdom biofilm associated with ECC, indicating that EPS inhibitors may be required for enhanced killing efficacy and optimal anti-biofilm activity, which could have therapeutic implications for other bacterial-fungal infections.

Student Presenter

This abstract is based on research that was funded entirely or partially by an outside source:
Supported in part by grants from NIH DE025220

Disclosure Statement:
The submitter must disclose the names of the organizations with which any author have a relationship, the nature of the relationship, and the clinical or research area involved. The following is submitted: NONE

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