ArticlePLoS genetics2019
Attenuating the emergence of anti-fungal drug resistance by harnessing synthetic lethal interactions in a model organism.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Pooled CRISPRi screening reveals fungal-specific drug target candidates.Nature microbiology · 2026Article
- Antifungal resistance: from classical mechanisms to the expanding role of acetyltransferases.Journal of biomedical science · 2026Review
- Pooled CRISPRi screening reveals fungal-specific vulnerabilities across environments and genetic backgrounds.bioRxiv : the preprint server for biology · 2026Article
- Leveraging synthetic genetic array screening to identify therapeutic targets and inhibitors for combatting azole resistance inMicrobiology spectrum · 2025Article
- Is a Fungal Apocalypse Inevitable or Just a Hallucination? An Overview of the Antifungal Armamentarium Used in the Fight against Pathogenic Fungi.ACS medicinal chemistry letters · 2025Review
- Antifungal drug resistance in Candida glabrata: role of cellular signaling and gene regulatory networks.FEMS yeast research · 2025Review
- New antifungal strategies and drug development against WHO critical priority fungal pathogens.Frontiers in cellular and infection microbiology · 2025Review
- Article
- Molecular mechanisms governing antifungal drug resistance.npj antimicrobials and resistance · 2023Review
- yEvo: experimental evolution in high school classrooms selects for novel mutations that impact clotrimazole resistance in Saccharomyces cerevisiae.G3 (Bethesda, Md.) · 2022Article
- Epigenetic Regulation of Antifungal Drug Resistance.Journal of fungi (Basel, Switzerland) · 2022Review
- Histone Acetylation Regulator Gcn5 Mediates Drug Resistance and Virulence of Candida glabrata.Microbiology spectrum · 2022Article
- Comprehensive genetic analysis of adhesin proteins and their role in virulence of Candida albicans.Genetics · 2021Article
- Genetic Basis of Azole and Echinocandin Resistance in Clinical Candida glabrata in Japan.Antimicrobial agents and chemotherapy · 2020Article
- The Quiet and Underappreciated Rise of Drug-Resistant Invasive Fungal Pathogens.Journal of fungi (Basel, Switzerland) · 2020Review
- Evolution of drug-resistant and virulent small colonies in phenotypically diverse populations of the human fungal pathogenProceedings. Biological sciences · 2020Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Drug resistance is a rapidly emerging concern, thus prompting the development of novel therapeutics or combinatorial therapy. Currently, combinatorial therapy targets are based on knowledge of drug mode of action and/or resistance mechanisms, constraining the number of target proteins. Unbiased genome-wide screens could reveal novel genetic components within interaction networks as potential targets in combination therapies. Testing this, in the context of antimicrobial resistance, we implemented an unbiased genome-wide screen, performed in Saccharomyces cerevisiae expressing a Candida glabrata PDR1+ gain-of-function allele. Gain-of-function mutations in this gene are the principal mediators of fluconazole resistance in this human fungal pathogen. Eighteen synthetically lethal S. cerevisiae genetic mutants were identified in cells expressing C. glabrata PDR1+. One mutant, lacking the histone acetyltransferase Gcn5, was investigated further. Deletion or drug-mediated inhibition of Gcn5 caused a lethal phenotype in C. glabrata cells expressing PDR1+ alleles. Moreover, deletion or drug-mediated inactivation of Gcn5, inhibited the emergence of fluconazole-resistant C. glabrata isolates in evolution experiments. Thus, taken together, the data generated in this study provides proof of concept that synthetically lethal genetic screens can identify novel candidate proteins that when therapeutically targeted could allow effective treatment of drug-resistant infections.
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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.