scholarly journals 4 / The antifungal mechanism of action for plant defensins is defined via treatment of a barcoded yeast deletion library.

2018 ◽  
Author(s):  
Kathy Parisi
Keyword(s):  
Mechanism Of Action ◽  
Antifungal Mechanism ◽  
Plant Defensins ◽  
Yeast Deletion Library ◽  
Deletion Library ◽  
Yeast Deletion

scholarly journals Plant defensins: types, mechanism of action and prospects of genetic engineering for enhanced disease resistance in plants

3 Biotech ◽  
2019 ◽  
Vol 9 (5) ◽  
Author(s):  
Raham Sher Khan ◽  
Aneela Iqbal ◽  
Radia Malak ◽  
Kashmala Shehryar ◽  
Syeda Attia ◽  
...  
Keyword(s):  
Disease Resistance ◽  
Genetic Engineering ◽  
Mechanism Of Action ◽  
Plant Defensins

scholarly journals Loss of the Homotypic Fusion and Vacuole Protein Sorting or Golgi-Associated Retrograde Protein Vesicle Tethering Complexes Results in Gentamicin Sensitivity in the Yeast Saccharomyces cerevisiae

2006 ◽  
Vol 50 (2) ◽  
pp. 587-595 ◽  
Author(s):  
Mark C. Wagner ◽  
Elizabeth E. Molnar ◽  
Bruce A. Molitoris ◽  
Mark G. Goebl
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Intracellular Trafficking ◽  
Protein Sorting ◽  
Growth Conditions ◽  
Yeast Saccharomyces Cerevisiae ◽  
Vesicle Tethering ◽  
Yeast Deletion Library ◽  
Texas Red ◽  
Deletion Library ◽  
Logarithmic Growth

ABSTRACT Gentamicin continues to be a primary antibiotic against gram-negative infections. Unfortunately, associated nephro- and ototoxicity limit its use. Our previous mammalian studies showed that gentamicin is trafficked to the endoplasmic reticulum in a retrograde manner and subsequently released into the cytosol. To better dissect the mechanism through which gentamicin induces toxicity, we have chosen to study its toxicity using the simple eukaryote Saccharomyces cerevisiae. A recent screen of the yeast deletion library identified multiple gentamicin-sensitive strains, many of which participate in intracellular trafficking. Our approach was to evaluate gentamicin sensitivity under logarithmic growth conditions. By quantifying growth inhibition in the presence of gentamicin, we determined that several of the sensitive strains were part of the Golgi-associated retrograde protein (GARP) and homotypic fusion and vacuole protein sorting (HOPS) complexes. Further evaluation of their other components showed that the deletion of any GARP member resulted in gentamicin-hypersensitive strains, while the deletion of other HOPS members resulted in less gentamicin sensitivity. Other genes whose deletion resulted in gentamicin hypersensitivity included ZUO1, SAC1, and NHX1. Finally, we utilized a Texas Red gentamicin conjugate to characterize gentamicin uptake and localization in both gentamicin-sensitive and -insensitive strains. These studies were consistent with our mammalian studies, suggesting that gentamicin toxicity in yeast results from alterations to intracellular trafficking pathways. The identification of genes whose absence results in gentamicin toxicity will help target specific pathways and mechanisms that contribute to gentamicin toxicity.

scholarly journals Antifungal Mechanism of Action of Lauryl Betaine Against Skin-Associated FungusMalassezia restricta

Mycobiology ◽  
2019 ◽  
Vol 47 (2) ◽  
pp. 242-249
Author(s):  
Eunsoo Do ◽  
Hyun Gee Lee ◽  
Minji Park ◽  
Yong-Joon Cho ◽  
Dong Hyeun Kim ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Antifungal Mechanism

scholarly journals Chemical genetic analyses of compounds derived from feijoa fruit

2021 ◽  
Author(s):  
◽  
Mona Mokhtari
Keyword(s):  
Antifungal Activity ◽  
Mechanism Of Action ◽  
Antifungal Drugs ◽  
Chemical Diversity ◽  
Zinc Homeostasis ◽  
Genetic Profile ◽  
Antifungal Compounds ◽  
Genetic Analyses ◽  
Antifungal Mechanism ◽  
Chemical Genetic

<p>Nature has been a rich source of pharmaceutical compounds, producing 80% of our currently prescribed drugs. The feijoa plant, Acca sellowiana, is classified in the family Myrtaceae, native to South America, and currently grown worldwide to produce feijoa fruit. Compounds with anticancer, anti-inflammatory, antibacterial and antifungal activities have been isolated from feijoa; however, the diversity of these compounds is not known nor is the mechanism of action of any of these compounds. I hypothesized that identifying compounds in novel feijoa cultivars would improve our understanding of the chemical diversity of antifungal compounds in feijoa and determining the antifungal mechanism of action of feijoa compounds would provide insight into the pharmaceutical potential of these compounds. First, GC-MS analyses were used to obtain an unbiased profile of 151 compounds from 16 cultivars of feijoa, of which six were novel cultivars. Multivariate analysis distinguished 18 compounds that were significantly and positively correlated to antifungal activity based on growth inhibition of Saccharomyces cerevisiae, of which seven had not previously been described from feijoa. Two novel cultivars were identified as the most bioactive cultivars, and the compound 4-cyclopentene-1,3-dione found in a couple of cultivars was potently antifungal against human pathogenic isolates of four Candida species. Second, chemical genetic analyses were used to investigate the mechanism of action of estragole, an antifungal compound previously isolated from feijoa. The chemical genetic profile of estragole was distinct from that of other known antifungal compounds, suggesting the mechanism of action of estragole has a novel antifungal mechanism. Third, chemical genetic analyses were used to investigate the mechanism of action of an ethanol adduct of vescalagin (EtOH-vescalagin) isolated from feijoa. We showed EtOH-vescalagin is antifungal against human pathogenic strains. Genome-wide chemical genetic analyses of EtOH-vescalagin indicated antifungal activity is mediated by disruptions of iron homeostasis, zinc homeostasis and retromer recycling through iron chelation. Overall, these results indicate the chemical and biological value of feijoa as a source of antifungal drugs.</p>

scholarly journals Chemical genetic analyses of compounds derived from feijoa fruit

2021 ◽  
Author(s):  
◽  
Mona Mokhtari
Keyword(s):  
Antifungal Activity ◽  
Mechanism Of Action ◽  
Antifungal Drugs ◽  
Chemical Diversity ◽  
Zinc Homeostasis ◽  
Genetic Profile ◽  
Antifungal Compounds ◽  
Genetic Analyses ◽  
Antifungal Mechanism ◽  
Chemical Genetic

<p>Nature has been a rich source of pharmaceutical compounds, producing 80% of our currently prescribed drugs. The feijoa plant, Acca sellowiana, is classified in the family Myrtaceae, native to South America, and currently grown worldwide to produce feijoa fruit. Compounds with anticancer, anti-inflammatory, antibacterial and antifungal activities have been isolated from feijoa; however, the diversity of these compounds is not known nor is the mechanism of action of any of these compounds. I hypothesized that identifying compounds in novel feijoa cultivars would improve our understanding of the chemical diversity of antifungal compounds in feijoa and determining the antifungal mechanism of action of feijoa compounds would provide insight into the pharmaceutical potential of these compounds. First, GC-MS analyses were used to obtain an unbiased profile of 151 compounds from 16 cultivars of feijoa, of which six were novel cultivars. Multivariate analysis distinguished 18 compounds that were significantly and positively correlated to antifungal activity based on growth inhibition of Saccharomyces cerevisiae, of which seven had not previously been described from feijoa. Two novel cultivars were identified as the most bioactive cultivars, and the compound 4-cyclopentene-1,3-dione found in a couple of cultivars was potently antifungal against human pathogenic isolates of four Candida species. Second, chemical genetic analyses were used to investigate the mechanism of action of estragole, an antifungal compound previously isolated from feijoa. The chemical genetic profile of estragole was distinct from that of other known antifungal compounds, suggesting the mechanism of action of estragole has a novel antifungal mechanism. Third, chemical genetic analyses were used to investigate the mechanism of action of an ethanol adduct of vescalagin (EtOH-vescalagin) isolated from feijoa. We showed EtOH-vescalagin is antifungal against human pathogenic strains. Genome-wide chemical genetic analyses of EtOH-vescalagin indicated antifungal activity is mediated by disruptions of iron homeostasis, zinc homeostasis and retromer recycling through iron chelation. Overall, these results indicate the chemical and biological value of feijoa as a source of antifungal drugs.</p>

scholarly journals Activator Gcn4p and Cyc8p/Tup1p Are Interdependent for Promoter Occupancy at ARG1 In Vivo

2005 ◽  
Vol 25 (24) ◽  
pp. 11171-11183 ◽  
Author(s):  
Soon-ja Kim ◽  
Mark J. Swanson ◽  
Hongfang Qiu ◽  
Chhabi K. Govind ◽  
Alan G. Hinnebusch
Keyword(s):  
Amino Acid ◽  
Rna Polymerase Ii ◽  
Transcriptional Activation ◽  
Target Genes ◽  
Direct Role ◽  
Valine Biosynthesis ◽  
Promoter Occupancy ◽  
Yeast Deletion Library ◽  
Deletion Library

ABSTRACT The Cyc8p/Tup1p complex mediates repression of diverse genes in Saccharomyces cerevisiae and is recruited by DNA binding proteins specific for the different sets of repressed genes. By screening the yeast deletion library, we identified Cyc8p as a coactivator for Gcn4p, a transcriptional activator of amino acid biosynthetic genes. Deletion of CYC8 confers sensitivity to an inhibitor of isoleucine/valine biosynthesis and impairs activation of Gcn4p-dependent reporters and authentic amino acid biosynthetic target genes. Deletion of TUP1 produces similar but less severe activation defects in vivo. Although expression of Gcn4p is unaffected by deletion of CYC8, chromatin immunoprecipitation assays reveal a strong defect in binding of Gcn4p at the target genes ARG1 and ARG4 in cyc8Δ cells and to a lesser extent in tup1Δ cells. The defects in Gcn4p binding and transcriptional activation in cyc8Δ cells cannot be overcome by Gcn4p overexpression but are partially suppressed in tup1Δ cells. The impairment of Gcn4p binding in cyc8Δ and tup1Δ cells is severe enough to reduce recruitment of SAGA, Srb mediator, TATA binding protein, and RNA polymerase II to the ARG1 and ARG4 promoters, accounting for impaired transcriptional activation of these genes in both mutants. Cyc8p and Tup1p are recruited to the ARG1 and ARG4 promoters, consistent with a direct role for this complex in stimulating Gcn4p occupancy of the upstream activation sequence (UAS). Interestingly, Gcn4p also stimulates binding of Cyc8p/Tup1p at the 3′ ends of these genes, raising the possibility that Cyc8p/Tup1p influences transcription elongation. Our findings reveal a novel coactivator function for Cyc8p/Tup1p at the level of activator binding and suggest that Gcn4p may enhance its own binding to the UAS by recruiting Cyc8p/Tup1p.

scholarly journals Biofilm eradication and antifungal mechanism of action against Candida albicans of cationic dicephalic surfactants with a labile linker

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Emil Paluch ◽  
Jakub Szperlik ◽  
Łukasz Lamch ◽  
Kazimiera A. Wilk ◽  
Ewa Obłąk
Keyword(s):  
Candida Albicans ◽  
Mechanism Of Action ◽  
Surface Coating ◽  
Opportunistic Pathogen ◽  
Cell Membrane Permeability ◽  
Strong Interactions ◽  
Alkyl Chains ◽  
Antifungal Mechanism ◽  
Quaternary Ammonium Group ◽  
Antibiofilm Agents

AbstractOur research aims to expand the knowledge on relationships between the structure of cationic dicephalic surfactants—N,N-bis[3,3_-(dimethylamine)propyl]alkylamide dihydrochlorides and N,N-bis[3,3_-(trimethylammonio)propyl]alkylamide dibromides (alkyl: n-C9H19, n-C11H23, n-C13H27, n-C15H31)—and their antifungal mechanism of action on Candida albicans. The mentioned groups of amphiphilic substances are characterized by the presence of a weak, hydrochloride cationic center readily undergoing deprotonation, as well as a stable, strong quaternary ammonium group and alkyl chains capable of strong interactions with fungal cells. Strong fungicidal properties and the role in creation and eradication of biofilm of those compounds were discussed in our earlier works, yet their mechanism of action remained unclear. It was shown that investigated surfactants induce strong oxidative stress and cause increase in cell membrane permeability without compromising its continuity, as indicated by increased potassium ion (K+) leakage. Thus experiments carried out on the investigated opportunistic pathogen indicate that the mechanism of action of the researched surfactants is different than in the case of the majority of known surfactants. Results presented in this paper significantly broaden the understanding on multifunctional cationic surfactants and their mechanism of action, as well as suggest their possible future applications as surface coating antiadhesives, fungicides and antibiofilm agents in medicine or industry.

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