Isoeugenol Affects Expression Pattern of Conidial Hydrophobin Gene RodA and Transcriptional Regulators MedA and SomA Responsible for Adherence and Biofilm Formation in Aspergillus fumigatus

Abstract

Aspergillus fumigatus is one of the major pathogenic fungal species, causing life-threatening infections. Due to a limited spectrum of available antifungals, exploration of new drug targets as well as potential antifungal molecules has become pertinent. Rodlet layer plays an important role in adherence of fungal conidia to hydrophobic cell surfaces in host, which also leads to A. fumigatus biofilm formation, contributing factor to fungal pathogenicity. From decades, natural sources have been known for the development of new active molecules. The present study investigates effect of isoeugenol on genes responsible for hydrophobins (RodA), adhesion as well as biofilm formation (MedA and SomA) of A. fumigatus. Minimum inhibitory concentrations (MIC and IC50) of isoeugenol against A. fumigatus were determined using broth microdilution assay. The IC50 results showed reduced hydrophobicity and biofilm formation after treatment with the compound and electron micrograph data corroborated these findings. The qRT-PCR showed a significant downregulation of genes RodA, MedA, SomA and pksP involved in hydrophobicity and biofilm formation. SwissADME studies potentiated drug-like propensity for isoeugenol which formed four hydrogen bonds with low binding energy (-4.54 Kcal/mol) at the catalytic site of RodA protein studied via AutoDock4. Hence, the findings conclude that isoeugenol inhibits conidial hydrophobicity and biofilm formation of A. fumigatus and further investigations are warranted in this direction.

4-Allyl-2-methoxyphenol modulates the expression of genes involved in efflux pump, biofilm formation and sterol biosynthesis in azole resistant Aspergillus fumigatus

“…In our study, the overexpression of the MDR4 gene suggested that this gene is linked with ITC resistance and after eugenol treatment gene expression was decreased. Further, transcription regulatory genes MedA and SomA were downregulated in all the eugenol-treated ARAF isolates except B19 and R03 for MedA gene expression and similar results were reported by Gupta et al (2022) for the downregulation of MedA and SomA genes in presence of isoeugenol. Further, mfsC gene expression analysis showed that the gene was downregulated in the four treated ARAF isolates (B19, RT28, B03 and RB01).…”

“…Ten azole-resistant A.fumigatus isolates (eugenol-treated and untreated) along with a susceptible A.fumigatus (ATCC 46645; control) isolates were investigated for the expression analysis of the genes of interest by quantitative real time PCR (qRT-PCR; Gupta et al, 2022). Two micrograms of total RNA were reverse transcribed into first-stand cDNA using the Hi-cDNA synthesis kit (HiMedia, India) by following the manufacturer's recommendations.…”

Gene expression, molecular docking, and molecular dynamics studies to identify potential antifungal compounds targeting virulence proteins/genes VelB and THR as possible drug targets against Curvularia lunata

“…The expression of the genes of interest was quantified by quantitative real time-PCR (qRT-PCR) (Gupta et al, 2019(Gupta et al, , 2022. Mycelial cultures were harvested, and RNA was extracted using TRIzol ™ reagent (Invitrogen).…”