ArticlePloS one2011
High-throughput screen for identifying small molecules that target fungal zinc homeostasis.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
14 citing papers in PubMed, 34 citations in OpenAlex.
- Lansoprazole interferes with fungal respiration and acts synergistically with amphotericin B against multidrug-resistantEmerging microbes & infections · 2024Article
- Luciferase-Based High-Throughput Screen with Aspergillus fumigatus to Identify Antifungal Small Molecules.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Antifungal drug screening: thinking outside the box to identify novel antifungal scaffolds.Current opinion in microbiology · 2020Review
- Transcription factors and transporters in zinc homeostasis: lessons learned from fungi.Critical reviews in biochemistry and molecular biology · 2020Review
- The intersection of host and fungus through the zinc lens.Current opinion in microbiology · 2019Review
- Zinc and Iron Homeostasis: Target-Based Drug Screening as New Route for Antifungal Drug Development.Frontiers in cellular and infection microbiology · 2019Article
- Atovaquone Impairs Growth of Aspergillus and Fusarium Keratitis Isolates by Modulating Mitochondrial Function and Zinc Homeostasis.Investigative ophthalmology & visual science · 2018Article
- Cyclic AMP Pathway Activation and Extracellular Zinc Induce Rapid Intracellular Zinc Mobilization inFrontiers in microbiology · 2018Article
- HcZrt2, a zinc responsive gene, is indispensable for the survival of Histoplasma capsulatum in vivo.Medical mycology · 2016Article
- Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing Fungal Drug Resistance and Morphogenesis.PLoS genetics · 2016Article
- Calcium Ions Tune the Zinc-Sequestering Properties and Antimicrobial Activity of Human S100A12.Chemical science · 2016Article
- Effects of zinc transporters on Cryptococcus gattii virulence.Scientific reports · 2015Article
- Competition for zinc binding in the host-pathogen interaction.Frontiers in cellular and infection microbiology · 2013Review
- Fluxes in "free" and total zinc are essential for progression of intraerythrocytic stages of Plasmodium falciparum.Chemistry & biology · 2012Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Resistance to traditional antifungal drugs has increased significantly over the past three decades, making identification of novel antifungal agents and new targets an emerging priority. Based on the extraordinary zinc requirement of several fungal pathogens and their well-established sensitivity to zinc deprivation, we developed an efficient cell-based screen to identify new antifungal drugs that target the zinc homeostasis machinery. The screen is based on the zinc-regulated transcription factor Zap1 of Saccharomyces cerevisiae, which regulates transcription of genes like the high-affinity zinc transporter ZRT1. We generated a genetically modified strain of S. cerevisae that reports intracellular zinc deficiency by placing the coding sequence of green fluorescent protein (GFP) under the control of the Zap1-regulated ZRT1 promoter. After showing that the GFP fluorescence signal correlates with low intracellular zinc concentrations in this strain, a protocol was developed for screening small-molecule libraries for compounds that induce Zap1-dependent GFP expression. Comparison of control compounds and known modulators of metal metabolism from the library reveals a robust screen (Z' = 0.74) and validates this approach to the discovery of new classes of antifungal compounds that interfere with the intracellular zinc homeostasis. Given that growth of many pathogenic organisms is significantly impaired by zinc limitation; these results identify new types of antifungal drugs that target critical nutrient acquisition pathways.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.