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 IC 50 ) of isoeugenol against A. fumigatus were determined using broth microdilution assay. The IC 50 results showed reduced hydrophobicity and biofilm formation as well as eradication 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. Supplementary Information The online version contains supplementary material available at 10.1007/s00203-022-02817-w.

Design and synthesis of eugenol/isoeugenol glycoconjugates and other analogues as antifungal agents against Aspergillus fumigatus

“…Similar results were reported in our previously published paper showing a significant decrease in DHN-melanin in A. fumigatus in the presence of isoeugenol. 12…”

“…Similar results were reported in our previously published paper showing a significant decrease in DHN-melanin in A. fumigatus in the presence of isoeugenol. 12 A significant reduction in the melanin content of 6i and 7 treated conidia with reference to eugenol and the positive control was observed. According to Kumar et al, 35 the absorption spectra showed characteristic absorption peaks in the UV region ranging from 265-290 nm, but not in the visible region.…”

“…9 Eugenol 1 and isoeugenol 2 interfere with microbial membrane functions (membrane binding and permeability alteration) or suppress virulence factors including toxins, enzymes, the melanin biosynthesis pathway, hydrophobins, and formation of biofilms. [10][11][12] They also induce the generation of H 2 O 2 and increase the free Ca 2+ concentration in the cytoplasm. Structural modifications in available drugs as well as naturally active lead moieties are conducted to enhance the drug efficacy and reduce their side effects.…”

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 , 2022 ). Mycelial cultures were harvested, and RNA was extracted using TRIzol™ reagent (Invitrogen).…”

Aspergillus Hydrophobins: Physicochemical Properties, Biochemical Properties, and Functions in Solid Polymer Degradation

“…A similar phenomenon has been reported for SC3 of S. commune ; disruption of disulfide bonds by a reducing agent and free thiol-blocking reagents abolishes rodlet formation by SC3 [ 133 ]. The phenylpropanoid isoeugenol inhibits rodlet formation by AfRodA on the conidial surface by decreasing the AfrodA transcription level and by interacting with the Cys residues of AfRodA [ 134 ].…”