Pogostone disrupts key virulence traits of Candida albicans: hyphal inhibition and biofilm suppression

Candida albicans (C. albicans) is an opportunistic mycopathogen that clinically presents serious challenges due to its ability to cause diverse infections. High mortality rates and increased resistance to antifungals are what make this pathogen particularly concerning. Pogostone (PO) is a bioactive compound with anti-C. albicans activity, isolated from Pogostemon cablin (patchouli). Yet, there is limited research concerning the mechanism of action of PO on C. albicans biofilms in a detailed and thorough manner. It is for this reason that this study sought to determine the inhibitory effects of PO on C. albicans biofilm and hyphae. PO displayed a noticeable inhibitory effect against fluconazole-resistant Candida species that had an MIC range of 16 to 32 µg/mL. Optical microscopy and scanning electron microscopy (SEM) observations revealed that PO effectively inhibited hyphal morphotransformation. The results obtained from XTT reduction assays, crystal violet (CV) staining, and cell surface hydrophobicity (CSH) measurements indicated that PO significantly reduces metabolic activity, biomass accumulation, and surface hydrophobicity of C. albicans biofilms across different growth stages. Additionally, the confocal laser scanning microscopy (CLSM) imaging further demonstrated PO’s interference in the three-dimensional architecture of C. albicans biofilms. Notably, this study innovatively discovered that PO can inhibit the adhesion and invasion of C. albicans on human vaginal epithelial (VK2/E6E7) cells. Transcriptome data showed that PO affected gene expression involved in hyphal morphogenesis, biofilm formation, and several major metabolic processes. The reduced expression of the virulence gene candidates HWP1, ECE1, ALS3, TPK2, and EFG1 was validated by qRT-PCR. The data point towards PO interfering with several biological pathways, especially ribosomal biopathways, metabolism, and gene transcription related to biofilm formation. PO exerts its antifungal activity against C. albicans by disrupting two major virulence factors: inhibition of mycelium and biofilm. This study provides a new insight into the mode of antifungal actions of PO and thus opens newer vistas for its use in alternative therapy against conventional antifungal therapies.