Lupeol mitigates biofilm formation and attenuates virulence dimorphism in Candida albicans

The global burden of Candida infections, especially in immunocompromised individuals, underscores the need for novel therapies. Candida's virulence is driven by traits like hyphal elongation and biofilm formation, making these key targets for managing candidiasis and preventing its progression to life-threatening systemic infections.

This study investigates the anticandidal efficacy of lupeol at sub-MIC levels against Candida albicans, Candida tropicalis, and Candida glabrata, focusing on its effects on biofilm formation, hyphal progression, and the expression of virulence genes.

The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of lupeol were determined against the Candida species. Sub-MIC concentrations (25-200 μg/mL) inhibited biofilm formation, as assessed by confocal and scanning electron microscopy. Lupeol's effects on hyphal progression and germ tube formation in C. albicans were evaluated, and qPCR analyzed key virulence gene expression.

The MIC and MFC of lupeol were found to be 256 and 512 μg/mL, respectively, against C. albicans, C. tropicalis, and C. glabrata. At sub-MIC levels, lupeol dose-dependently inhibited biofilm formation without affecting metabolic activity. It altered biofilm structure, inhibited hyphal growth, reversed hyphae to yeast morphology, and modified colony appearance. qPCR revealed downregulation of virulence genes (RAS1, UME6, HWP1, EFG1, CPH1) and upregulation of TUP1.

These findings highlight lupeol as a promising therapeutic candidate for combating Candida infections by targeting critical virulence factors and disrupting biofilm integrity. This study paves the way for further exploration of lupeol's clinical applications in antifungal therapy.