02462nas a2200241   4500008004100000022001400041245019400055210006900249260000800318300000800326490000800334520156100342653002601903653001901929653001501948653002901963653001401992100001802006700001502024700002802039700002602067856012702093       2022                        eng d  a0302-893300aIsoeugenol affects expression pattern of conidial hydrophobin gene RodA and transcriptional regulators MedA and SomA responsible for adherence and biofilm formation in Aspergillus fumigatus0 aIsoeugenol affects expression pattern of conidial hydrophobin ge  cAPR  a2140 v2043 a<p>
	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 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.</p>
10aAspergillus fumigatus10aHydrophobicity10aIsoeugenol10aTranscription regulators10aVirulence1 aGupta, Lovely1 aSen, Pooja1 aBhattacharya, Asish, K.1 aVijayaraghavan, Pooja  uhttp://library.ncl.res.in/content/isoeugenol-affects-expression-pattern-conidial-hydrophobin-gene-roda-and-transcriptional02990nas a2200277   4500008004100000022001400041245018800055210006900243260000900312490000800321520198600329653002602315653002402341653001202365653001902377653002902396653001402425100001802439700001902457700002102476700002102497700001502518700002802533700002602561856012502587       2024                        eng d  a1364-507200aUnveiling the cell wall-targeting mechanisms and multifaceted virulence modulation by a eugenol glycoconjugate against aspergillus fumigatus: insights from in vitro and in ovo studies0 aUnveiling the cell walltargeting mechanisms and multifaceted vir  cJAN 0 v1353 a<p>
	Aim The primary objective of this study was to elucidate the putative cell wall-associated targets of compound 6i, a glycoconjugate of eugenol, in Aspergillus fumigatus, while also evaluating its toxicity and assessing histopathologic alterations in the liver, heart, and kidney of compound 6i-treated embryos using an in ovo model.Method To achieve this aim, compound 6i was synthesized, and a series of biochemical assays were performed to determine its impact on the fungal cell wall. Additionally, quantitative real time-PCR and liquid chromatography-mass spectrometry/mass spectrometry analyses were conducted to investigate changes in gene and protein expression profiles associated with melanin biosynthesis, conidiation, siderophore production, transcriptional regulation of beta-glucan biosynthesis, and calcineurin activity in A. fumigatus.Results The experimental findings revealed that compound 6i exhibited notable antifungal activity against A. fumigatus by perturbing cell wall integrity, hindering ergosterol, glucan, and chitin biosynthesis, and inhibiting catalase production. Moreover, relative gene expression and proteomic analyses demonstrated that compound 6i exerted both downregulatory and upregulatory effects on several crucial genes and proteins involved in the aforementioned fungal processes. Furthermore, increased expression of oxidative stress-related proteins was observed in the presence of compound 6i. Notably, the glycoconjugate of eugenol did not elicit cytotoxicity in the liver, heart, and kidney of chick embryos.Conclusion The current investigation elucidated the multifaceted mechanisms by which compound 6i exerts its antifungal effects against A. fumigatus, primarily through targeting cell wall components and signaling pathways. These findings underscore the potential of the eugenol glycoconjugate as a promising antifungal candidate, warranting further exploration and development for combating A. fumigatus infections.</p>
10aAspergillus fumigatus10acell wall integrity10aEugenol10aGlycoconjugate10aTranscription regulators10aVirulence1 aGupta, Lovely1 aVerma, Shalini1 aGoswami, Lakshmi1 aKamboj, Himanshu1 aSen, Pooja1 aBhattacharya, Asish, K.1 aVijayaraghavan, Pooja  uhttp://library.ncl.res.in/content/unveiling-cell-wall-targeting-mechanisms-and-multifaceted-virulence-modulation-eugenol