ArticleThe Journal of biological chemistry2009
Chemical genetic profiling and characterization of small-molecule compounds that affect the biosynthesis of unsaturated fatty acids in Candida albicans.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 80 citations in OpenAlex.
- Review
- Systemic infection by Candida albicans requires FASN-α subunit induced cell wall remodeling to perturb immune response.PLoS pathogens · 2025Article
- A single gene mutation underpins metabolic adaptation and acquisition of filamentous competence in the emerging fungal pathogen Candida auris.PLoS pathogens · 2024Article
- Article
- Repurposing a human acetyl-CoA carboxylase inhibitor firsocostat to treat fungal candidiasis alone and in combination.Antimicrobial agents and chemotherapy · 2024Article
- Small molecule inhibitors of fungal Δ(9) fatty acid desaturase as antifungal agents againstFrontiers in cellular and infection microbiology · 2024Article
- Lipid-Centric Approaches in Combating Infectious Diseases: Antibacterials, Antifungals and Antivirals with Lipid-Associated Mechanisms of Action.Antibiotics (Basel, Switzerland) · 2023Review
- Identification of triazenyl indoles as inhibitors of fungal fatty acid biosynthesis with broad-spectrum activity.Cell chemical biology · 2023Article
- The Heat Shock Transcription Factor HsfA Plays a Role in Membrane Lipids Biosynthesis Connecting Thermotolerance and Unsaturated Fatty Acid Metabolism in Aspergillus fumigatus.Microbiology spectrum · 2023Article
- Inhibition of cell cycle-dependent hyphal and biofilm formation by a novel cytochalasin 19,20‑epoxycytochalasin Q in Candida albicans.Scientific reports · 2023Article
- Chemical-Genetic Approaches for Exploring Mode of Action of Antifungal Compounds in the Fungal Pathogen Candida albicans.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Antibody screening reveals antigenic proteins involved inFrontiers in cellular and infection microbiology · 2023Article
- Genomic Approaches to Antifungal Drug Target Identification and Validation.Annual review of microbiology · 2022Review
- Identification of Inhibitors of Fungal Fatty Acid Biosynthesis.ACS infectious diseases · 2021Article
- Advances in fungal chemical genomics for the discovery of new antifungal agents.Annals of the New York Academy of Sciences · 2021Review
- Article
- Campafungins: Inhibitors ofJournal of natural products · 2020Article
- New Insights inFrontiers in cellular and infection microbiology · 2020Review
- Chemogenomic Profiling of the Fungal Pathogen Candida albicans.Antimicrobial agents and chemotherapy · 2018Article
- High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance.PLoS biology · 2017Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The balance between saturated and unsaturated fatty acids plays a crucial role in determining the membrane fluidity. In the diploid fungal pathogen Candida albicans, the gene for fatty acid Delta9 desaturase, OLE1, is essential for viability. Using a reverse genetic approach, termed the fitness test, we identified a group of structurally related synthetic compounds that induce specific hypersensitivity of the OLE1(+/-) strain. Genetic repression of OLE1 and chemical inhibition by two selected compounds, ECC145 and ECC188, resulted in a marked decrease in the total unsaturated fatty acids and impaired hyphal development. The resulting auxotroph of both was suppressed by the exogenous monounsaturated fatty acids (16:1Delta9 and 18:1Delta9). These correlations suggest that both compounds affect the level of unsaturated fatty acids, likely by impairing Ole1p directly or indirectly. However, the residual levels of monounsaturated fatty acids (MUFAs) resulted from chemical inhibition were significantly higher than OLE1 repression, indicating even partial inhibition of MUFAs is sufficient to stop cellular proliferation. Although the essentiality of OLE1 was suppressed by MUFAs in vitro, we demonstrated that it was required for virulence in a murine model of systemic candidiasis even when the animals were supplemented with a high fat diet. Thus, the fungal fatty acid desaturase is an attractive antifungal drug target. Taking advantage of the inhibitors and the relevant conditional shut-off strains, we validated several chemical genetic interactions observed in the fitness test profiles that reveal novel genetic interactions between OLE1/unsaturated fatty acids and other cellular processes.
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