ArticleProceedings of the National Academy of Sciences of the United States of America2010
Pathway analysis of Candida albicans survival and virulence determinants in a murine infection model.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 131 citations in OpenAlex.
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- Adaptation of the tetracycline-repressible system for modulating the expression of essential genes inmSphere · 2025Article
- Targeting fungal lipid synthesis for antifungal drug development and potentiation of contemporary antifungals.npj antimicrobials and resistance · 2025Review
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- Uncovering the role of mitochondrial genome in pathogenicity and drug resistance in pathogenic fungi.Frontiers in cellular and infection microbiology · 2025Review
- Central Role of the Actomyosin Ring in Coordinating Cytokinesis Steps in Budding Yeast.Journal of fungi (Basel, Switzerland) · 2024Review
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- Small molecule inhibitors of fungal Δ(9) fatty acid desaturase as antifungal agents againstFrontiers in cellular and infection microbiology · 2024Article
- Identification of triazenyl indoles as inhibitors of fungal fatty acid biosynthesis with broad-spectrum activity.Cell chemical biology · 2023Article
- Developing novel antifungals: lessons from G protein-coupled receptors.Trends in pharmacological sciences · 2023Review
- Genomic Approaches to Antifungal Drug Target Identification and Validation.Annual review of microbiology · 2022Review
- Molecular analysis and essentiality of Aro1 shikimate biosynthesis multi-enzyme inLife science alliance · 2022Article
- The Set1 Histone H3K4 Methyltransferase Contributes to Azole Susceptibility in a Species-Specific Manner by Differentially Altering the Expression of Drug Efflux Pumps and the Ergosterol Gene Pathway.Antimicrobial agents and chemotherapy · 2022Article
- Virulence-related metabolism is activated inHorticulture research · 2022Article
- Novel Promising Antifungal Target Proteins for Conquering Invasive Fungal Infections.Frontiers in microbiology · 2022Review
- Downregulation of Essential Genes in the Fungal Pathogen Candida auris.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Riboflavin as a promising antimicrobial agent? A multi-perspective review.Current research in microbial sciences · 2022Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One potentially rich source of possible targets for antifungal therapy are those Candida albicans genes deemed essential for growth under the standard culture (i.e., in vitro) conditions; however, these genes are largely unexplored as drug targets because essential genes are not experimentally amenable to conventional gene deletion and virulence studies. Using tetracycline-regulatable promoter-based conditional mutants, we investigated a murine model of candidiasis in which repressing essential genes in the host was achieved. By adding doxycycline to the drinking water starting 3 days prior to (dox - 3D) or 2 days post (dox + 2D) infection, the phenotypic consequences of temporal gene inactivation were assessed by monitoring animal survival and fungal burden in prophylaxis and acute infection settings. Of 177 selected conditional shut-off strains tested, the virulence of 102 was blocked under both repressing conditions, suggesting that the corresponding genes are essential for growth and survival in a murine host across early and established infection periods. Among these genes were those previously identified as antifungal drug targets (i.e., FKS1, ERG1, and ERG11), verifying that this methodology can be used to validate potential new targets. We also identify genes either conditionally essential or dispensable for in vitro growth but required for survival and virulence, including those in late stage ergosterol synthesis, or early steps in fatty acid or riboflavin biosynthesis. This study evaluates the role of essential genes with respect to pathogen virulence in a large-scale, systems biology context, and provides a general method for gene target validation and for uncovering unexpected antimicrobial targets.
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