Catechol thwarts virulent dimorphism in Candida albicans and potentiates the antifungal efficacy of azoles and polyenes

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).

Deciphering the Mechanism of MRSA Targeting Copper(II) Complexes of NN2 Pincer-Type Ligands

“…The MIC of each compound against MRSA and C. albicans was determined by microbroth dilution according to the procedure described in the CSLI guidelines with minor modifications . In short, 1% of standard cell suspensions of these strains were added to the 96 μL plate with complexes of concentration 2–1024 μg/mL.…”

Evaluation of the Anti-Histoplasma capsulatum Activity of Indole and Nitrofuran Derivatives and Their Pharmacological Safety in Three-Dimensional Cell Cultures

“…The n-heptane layer (the upper phase of the mixture) was transferred to microtubes and brought to −20 °C overnight. The analyses were carried out in a spectrophotometer at a wavelength of 281 nm with an ultraviolet (UV) spectrum [ 51 , 58 , 59 , 60 , 61 ]. Standard curves were prepared with 95% purity ergosterol (Sigma-Aldrich Milano, Italy) at concentrations ranging from 75 to 10 µg/mL.…”

2,4-Diacetylphloroglucinol Modulates Candida albicans Virulence

“…The production of aspartyl protease (Sap) of the 1–3 subfamily was determined according to Jothi et al [ 20 ] with some modifications. Briefly, the C. albicans planktonic cells and biofilms were grown in a YPD medium supplemented with inhibitory or/and sub-inhibitory concentrations of 2,4-DAPG for 24 h. After incubation, the cell-free supernatant was collected by centrifugation at 8000× g rpm for 10 min.…”