ArticleAntimicrobial agents and chemotherapy2008
Differential azole antifungal efficacies contrasted using a Saccharomyces cerevisiae strain humanized for sterol 14 alpha-demethylase at the homologous locus.
Article in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Chemical Inhibition of Sterol Biosynthesis.Biomolecules · 2024Pooled it
- Novel yeast-based biosensor for environmental monitoring of tebuconazole.Applied microbiology and biotechnology · 2024Article
- Azole resistance in Aspergillus fumigatus- comprehensive review.Archives of microbiology · 2024Review
- Article
- Mutations inmBio · 2020Article
- New diphenylphosphane derivatives of ketoconazole are promising antifungal agents.Scientific reports · 2019Article
- Genomewide Elucidation of Drug Resistance Mechanisms for Systemically Used Antifungal Drugs Amphotericin B, Caspofungin, and Voriconazole in the Budding Yeast.Antimicrobial agents and chemotherapy · 2019Article
- Identification of 14-α-Lanosterol Demethylase (CYP51) in Scedosporium Species.Antimicrobial agents and chemotherapy · 2018Article
- Synthesis and Anticandidal Activity Evaluation of New Benzimidazole-Thiazole Derivatives.Molecules (Basel, Switzerland) · 2017Article
- Identification of Trypanocidal Activity for Known Clinical Compounds Using a New Trypanosoma cruzi Hit-Discovery Screening Cascade.PLoS neglected tropical diseases · 2016Article
- Transcriptomics Analysis of Candida albicans Treated with Huanglian Jiedu Decoction Using RNA-seq.Evidence-based complementary and alternative medicine : eCAM · 2016Article
- The clinical candidate VT-1161 is a highly potent inhibitor of Candida albicans CYP51 but fails to bind the human enzyme.Antimicrobial agents and chemotherapy · 2014Article
- Azole affinity of sterol 14α-demethylase (CYP51) enzymes from Candida albicans and Homo sapiens.Antimicrobial agents and chemotherapy · 2013Article
- Microbial cytochromes P450: biodiversity and biotechnology. Where do cytochromes P450 come from, what do they do and what can they do for us?Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2013Review
- The cellular roles of Ccr4-NOT in model and pathogenic fungi-implications for fungal virulence.Frontiers in genetics · 2013Article
- An enlarged, adaptable active site in CYP164 family P450 enzymes, the sole P450 in Mycobacterium leprae.Antimicrobial agents and chemotherapy · 2012Article
- Protein trafficking, ergosterol biosynthesis and membrane physics impact recombinant protein secretion in Pichia pastoris.Microbial cell factories · 2011Article
- Article
- Azole binding properties of Candida albicans sterol 14-alpha demethylase (CaCYP51).Antimicrobial agents and chemotherapy · 2010Article
- A clinical isolate of Candida albicans with mutations in ERG11 (encoding sterol 14alpha-demethylase) and ERG5 (encoding C22 desaturase) is cross resistant to azoles and amphotericin B.Antimicrobial agents and chemotherapy · 2010Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Inhibition of sterol-14 alpha-demethylase, a cytochrome P450 (CYP51, Erg11p), is the mode of action of azole antifungal drugs, and with high frequencies of fungal infections new agents are required. New drugs that target fungal CYP51 should not inhibit human CYP51, although selective inhibitors of the human target are also of interest as anticholesterol agents. A strain of Saccharomyces cerevisiae that was humanized with respect to the amino acids encoded at the CYP51 (ERG11) yeast locus (BY4741:huCYP51) was produced. The strain was validated with respect to gene expression, protein localization, growth characteristics, and sterol content. The MIC was determined and compared to that for the wild-type parental strain (BY4741), using clotrimazole, econazole, fluconazole, itraconazole, ketoconazole, miconazole, and voriconazole. The humanized strain showed up to >1,000-fold-reduced susceptibility to the orally active azole drugs, while the topical agents showed no difference. Data from growth kinetic measurements substantiated this finding but also revealed reduced effectiveness against the humanized strain for the topical drugs. Cellular sterol profiles reflected the decreased susceptibility of BY4741:huCYP51 and showed a smaller depletion of ergosterol and accumulation of 14 alpha-methyl-ergosta-8, 24(28)-dien-3beta-6 alpha-diol than the parental strain under the same treatment conditions. This strain provides a useful tool for initial specificity testing for new drugs targeting CYP51 and clearly differentiates azole antifungals in a side-by-side comparison.
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