ArticleMolecular microbiology2017
Extensive functional redundancy in the regulation of Candida albicans drug resistance and morphogenesis by lysine deacetylases Hos2, Hda1, Rpd3 and Rpd31.
Article in Molecular microbiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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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
31 citing papers in PubMed, 44 citations in OpenAlex.
- F2F-202, a Selective Histone Deacetylase 6 (HDAC6) Inhibitor, Behaves as an Arrow with Multiple Tips against Azole-ResistantACS infectious diseases · 2026Article
- The Rpd3 histone deacetylase is a critical regulator of temperature-mediated morphogenesis and virulence in the human fungal pathogen Histoplasma.PLoS biology · 2026Article
- Epigenetic regulation of pathogenicity in fungi.Current genetics · 2025Review
- Potential role of lysine acetylation in the stepwise adaptation ofMicrobiology spectrum · 2025Article
- Protein lysine acetylation regulates oral microorganisms.Frontiers in cellular and infection microbiology · 2025Review
- Article
- Allosteric inhibition of tRNA synthetase Gln4 by N-pyrimidinyl-β-thiophenylacrylamides exerts highly selective antifungal activity.Cell chemical biology · 2024Article
- Roles of Hsp90 in Candida albicans morphogenesis and virulence.Current opinion in microbiology · 2023Review
- Post-transcriptional control of antifungal resistance in human fungal pathogens.Critical reviews in microbiology · 2023Review
- Synthetic Cinnamides and Cinnamates: Antimicrobial Activity, Mechanism of Action, and In Silico Study.Molecules (Basel, Switzerland) · 2023Article
- Epigenetic Regulation of Antifungal Drug Resistance.Journal of fungi (Basel, Switzerland) · 2022Review
- Genetic Structure and Triazole Antifungal Susceptibilities of Alternaria alternata from Greenhouses in Kunming, China.Microbiology spectrum · 2022Article
- High-Throughput Chemical Screen Identifies a 2,5-Disubstituted Pyridine as an Inhibitor of Candida albicans Erg11.mSphere · 2022Article
- The role ofiScience · 2022Review
- Novel Promising Antifungal Target Proteins for Conquering Invasive Fungal Infections.Frontiers in microbiology · 2022Review
- The SAGA and NuA4 component Tra1 regulates Candida albicans drug resistance and pathogenesis.Genetics · 2021Article
- Fungal Lysine Deacetylases in Virulence, Resistance, and Production of Small Bioactive Compounds.Genes · 2021Review
- Antifungal Drug Resistance: Molecular Mechanisms inChemical reviews · 2021Review
- Post-Translational Modifications Drive Success and Failure of Fungal-Host Interactions.Journal of fungi (Basel, Switzerland) · 2021Review
- Identification and Phenotypic Characterization of Hsp90 Phosphorylation Sites That Modulate Virulence Traits in the Major Human Fungal PathogenFrontiers in cellular and infection microbiology · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Current treatment efforts for fungal infections are hampered by the limited availability of antifungal drugs and by the emergence of drug resistance. A powerful strategy to enhance the efficacy of antifungal drugs is to inhibit the molecular chaperone Hsp90. Hsp90 governs drug resistance, morphogenesis and virulence in a leading fungal pathogen of humans, Candida albicans. Our previous work with Saccharomyces cerevisiae established acetylation as a novel mechanism of posttranslational control of Hsp90 function in fungi. We implicated lysine deacetylases (KDACs) as key regulators of resistance to the most widely deployed class of antifungals, the azoles, in both S. cerevisiae and C. albicans. Here, we demonstrate high levels of functional redundancy among the KDACs that are important for regulating Hsp90 function. We identify Hos2, Hda1, Rpd3 and Rpd31 as the KDACs mediating azole resistance and morphogenesis in C. albicans. Furthermore, we identify lysine 30 and 271 as critical acetylation sites on C. albicans Hsp90, and substitutions at these residues compromise Hsp90 function. Finally, we show that pharmacological inhibition of KDACs phenocopies pharmacological inhibition of Hsp90 and abrogates Hsp90-dependent azole resistance in numerous Candida species. This work illuminates new facets to the impact of KDACs on fungal drug resistance and morphogenesis, provides important insights into the divergence of the C. albicans Hsp90 regulatory network and reveals new targets for development of antifungal drugs.
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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.