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Mechanistic Assessment of Polyols in Combination with Model Antifungal Agents on Candida albicans Biofilms
Secondary Supervisor(s): Professor Rebecca Drummond
University of Registration: University of Birmingham
BBSRC Research Themes:
Project Outline
Fungal infections impact billions worldwide and pose a major challenge in infectious disease management, particularly due to rising fungal resistance and limited antifungal therapies. Candida albicans, the primary etiological agent of oral thrush and invasive candidiasis, demonstrates multiple virulence mechanisms including biofilm formation. Although nystatin and azole antifungals are frequently administered, resistance rates continue to rise. Furthermore, the poor solubility and low permeability of nystatin restrict its bioavailability and therapeutic efficacy (Sousa et al., 2023).
Our previous research has shown that multifunctional excipients, including amino acids and polyols inhibit microbial biofilms. Specifically, D-Glu and D-Asp bind to extracellular DNA, which weakens the extracellular matrix and allows antibiotics to penetrate and eliminate bacteria (Warraich et al., 2020). Additionally, a recent study found that polyols combined with chlorhexidine exhibit synergistic activity against S.mutans and C.albicans biofilms.
This project aims to investigate the mechanistic basis of polyols in combination with chlorhexidine and model antifungal agents on C.albicans biofilms. To achieve this, temporal analysis of biofilm disruption in the presence of polyols will be conducted using dynamic biofilm models. Mechanistic studies will utilise Candida mutant strains that are defective in biofilm formation and host invasion. The impact of polyols on virulence factors, including the expression of genes will be evaluated using qPCR. The architecture of fungal biofilms will be examined with matrix-specific stains using CLSM. FTIR will be used to study molecular interactions between polyols and antifungals. Finally, the most effective antifungal-polyol formulations will be developed in the approved GMP facilities at Quest Pharma Ltd. The primary outcome will be the development of novel antifungal combinations exhibiting enhanced efficacy based on mechanistic evaluation.