ArticleAntimicrobial agents and chemotherapy2001
In vitro and in vivo effects of 14alpha-demethylase (ERG11) depletion in Candida glabrata.
Article in Antimicrobial agents and chemotherapy, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Candida glabrata YPK2 is a multidrug susceptibility locus.Genetics · 2026Article
- Article
- Chitosan nanoparticles loaded with ribavirin, carboplatin, and thyme oil downregulate SNQ2, ERG11, CDR1, and MDR1 in Candida strains.Scientific reports · 2025Article
- Pan-drug resistance and hypervirulence in a human fungal pathogen are enabled by mutagenesis induced by mammalian body temperature.Nature microbiology · 2024Article
- Disclosing azole resistance mechanisms in resistant Candida glabrata strains encoding wild-type or gain-of-function CgPDR1 alleles through comparative genomics and transcriptomics.G3 (Bethesda, Md.) · 2022Article
- Exhibition of antifungal resistance by sterol-auxotrophic strains ofJAC-antimicrobial resistance · 2022Article
- Combining Colistin and Fluconazole Synergistically Increases Fungal Membrane Permeability and Antifungal Cidality.ACS infectious diseases · 2021Article
- Candida glabrata Transcription Factor Rpn4 Mediates Fluconazole Resistance through Regulation of Ergosterol Biosynthesis and Plasma Membrane Permeability.Antimicrobial agents and chemotherapy · 2020Article
- Article
- Generational distribution of a Candida glabrata population: Resilient old cells prevail, while younger cells dominate in the vulnerable host.PLoS pathogens · 2017Article
- Comparison of sterol import under aerobic and anaerobic conditions in three fungal species, Candida albicans, Candida glabrata, and Saccharomyces cerevisiae.Eukaryotic cell · 2013Article
- Systems-level antimicrobial drug and drug synergy discovery.Nature chemical biology · 2013Article
- Facultative sterol uptake in an ergosterol-deficient clinical isolate of Candida glabrata harboring a missense mutation in ERG11 and exhibiting cross-resistance to azoles and amphotericin B.Antimicrobial agents and chemotherapy · 2012Article
- Pathway analysis of Candida albicans survival and virulence determinants in a murine infection model.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- A gain-of-function mutation in the transcription factor Upc2p causes upregulation of ergosterol biosynthesis genes and increased fluconazole resistance in a clinical Candida albicans isolate.Eukaryotic cell · 2008Article
- Essential gene identification and drug target prioritization in Aspergillus fumigatus.PLoS pathogens · 2007Article
- Biology of the pathogenic yeast Candida glabrata.Folia microbiologica · 2006Review
- Targeted gene disruption of the 14-alpha sterol demethylase (cyp51A) in Aspergillus fumigatus and its role in azole drug susceptibility.Antimicrobial agents and chemotherapy · 2005Article
- Posaconazole is a potent inhibitor of sterol 14alpha-demethylation in yeasts and molds.Antimicrobial agents and chemotherapy · 2004Article
- Candida glabrata erg1 mutant with increased sensitivity to azoles and to low oxygen tension.Antimicrobial agents and chemotherapy · 2004Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sterol 14alpha-demethylase (ERG11) is the target enzyme of azole antifungals that are widely used for the treatment of fungal infections. Candida glabrata is known to be less susceptible to fluconazole than most Candida albicans strains, and the incidence of C. glabrata infection has been increasing mostly in conjunction with the use of azole antifungals. Recently, it has been reported that C. glabrata can rescue the defect of ergosterol biosynthesis by incorporating cholesterol from serum. To explore the effect of inactivating Erg11p in C. glabrata, we generated mutant strains in which the ERG11 gene was placed under the control of tetracycline-regulatable promoters. In these mutants, expression of the ERG11 gene can be repressed by doxycycline (DOX). All mutants showed a growth defect in the presence of DOX. The numbers of CFU of the mutants were lowered by only 1/10 with DOX treatment. In these mutants, accumulation of 4,14-dimethylzymosterol, which differs from an accumulated abnormal sterol detected in C. albicans and Saccharomyces cerevisiae treated with fluconazole, was observed by DOX treatment. Although such phenotypes were also observed in serum-containing media by DOX treatment, they were alleviated. Furthermore, the mutant could grow in DOX-treated mice without a severe reduction in the number of cells. Thus, depleting the expression of the ERG11 gene lowered the number of CFU by only 1/10 due to the accumulation of 4,14-demethylzymosterol in vitro, and it did not result in the defective growth of fungal cells in mice. These results suggested that Erg11p is not an ideal target molecule of antifungals for C. glabrata.
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