Abstract
The present study was deliberately focused to explore the antivirulence efficacy of a plant allelochemical—catechol against Candida albicans, and attempts were made to elucidate the underlying mechanisms as well. Catechol at its sub-MIC concentrations (2–256 μg/mL) exhibited a dose dependent biofilm as well as hyphal inhibitory efficacies, which were ascertained through both light and fluorescence microscopic analyses. Further, sub-MICs of catechol displayed remarkable antivirulence efficacy, as it substantially inhibited C. albicans’ virulence enzymes i.e. secreted hydrolases. Notably, FTIR analysis divulged the potency of catechol in effective loosening of C. albicans’ exopolymeric matrix, which was further reinforced using EPS quantification assay. Although, catechol at BIC (256 μg/mL) did not disrupt the mature biofilms of C. albicans, their initial adherence was significantly impeded by reducing their hydrophobic nature. Besides, FTIR analysis also unveiled the ability of catechol in enhancing the production of farnesol—a metabolite of C. albicans, whose accumulation naturally blocks yeast-hyphal transition. The qPCR data showed significant down-regulation of candidate genes viz., RAS1, HWP1 and ALS3 which are the key targets of Ras-cAMP-PKA pathway -the pathway that contribute for C. albicans’ pathogenesis. Interestingly, the up-regulation of TUP1 (a gene responsible for farnesol-mediated hyphal inhibition) during catechol exposure strengthen the speculation of catechol triggered farnesol-mediated hyphal inhibition. Furthermore, catechol profusely enhanced the fungicidal efficacy of certain known antifungal agent’s viz., azoles (ketoconazole and miconazole) and polyenes (amphotericin-B and nystatin).
Highlights
The present study was deliberately focused to explore the antivirulence efficacy of a plant allelochemical—catechol against Candida albicans, and attempts were made to elucidate the underlying mechanisms as well
Apart from morphological plasticity, myriad of factors including metabolic adaptability, biofilm formation, contact sensing and thigmotropism contributes to the pathogenesis of C. albicans[14]
We found catechol, one of the simplest allelochemicals rich in onions, maple and oak, as the promising antivirulence agents targeting biofilm and hyphal formation in C. albicans
Summary
The present study was deliberately focused to explore the antivirulence efficacy of a plant allelochemical—catechol against Candida albicans, and attempts were made to elucidate the underlying mechanisms as well. They can be able to cause irreversible pathogenic effect ranging from superficial to life-threatening systemic infections through its intrinsic yeast-to-hyphal transforming a bility[9]. In order to address the above-mentioned scientific issues, therapies that target virulence rather than harming the fungal metabolism have been proved to be even more promising One such remarkable approach is the antivirulence therapy, wherein biomolecules with proficiency to exclusively hamper the virulence traits of pathogens have been envisaged with the certainty that it would nullify the phenomenon of resistance by counteracting selection p ressure[16]. The present study was consciously aimed to explore and delineate the inhibitory efficacy of catechol against biofilm assemblage, hyphal transition and secreted virulence in C. albicans
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