Impact of Randomly Methylated Cyclodextrins on Candida albicans: Biofilm Formation, Morphogenesis and Oxidative Stress

Abstract

The challenges related to biofilm-associated infections and diseases have prompted scientists to identify the factors responsible for the formation of biofilms and to develop strategies aimed at decreasing biofilm-formation capacity.
The present study aimed to evaluate the effect of randomly methylated cyclodextrin derivatives, at concentrations ranging from 32 nM to 12.5 mM, on the capacity of Candida albicans to form biofilms at 37 °C over a period of 24 h.
This study provides novel insights into how randomly methylated α-cyclodextrin (RAMEA), randomly methylated β-cyclodextrin (RAMEB), and randomly methylated γ-cyclodextrin (RAMEG) can modulate C. albicans biofilm formation. Using the crystal violet assay and the XTT reduction assay, we consistently demonstrated that RAMEA and RAMEG have a clear, concentration-dependent inhibitory effect on both the total biofilm biomass and the metabolic activity of the cells associated with these biofilms. RAMEB exhibited a biphasic effect: low to moderate concentrations significantly reduced biofilm formation, while higher doses unexpectedly resulted in increased biofilm formation. Microscopic analysis revealed that elevated cyclodextrin concentrations induced hyphal formation. Optical density measurements and a membrane permeability assay indicated that none of the cyclodextrins had a notable cytotoxic effect or damaged the cell membrane. Moreover, elevated intracellular ROS levels were detected, suggesting a potential stress-inducing effect. These findings enhance our understanding of the complex interactions between cyclodextrin derivatives and fungal cells, underscoring their potential as biofilm-modulating agents.