ArticleAntimicrobial agents and chemotherapy1999
The ATP binding cassette transporter gene CgCDR1 from Candida glabrata is involved in the resistance of clinical isolates to azole antifungal agents.
Article in Antimicrobial agents and chemotherapy, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 166 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
166 citing papers in PubMed, 342 citations in OpenAlex.
- Cryo-EM structures of Cdr1 reveal snapshots of substrate transport and diverse inhibitor recognition.Science advances · 2026Article
- Experimental Evolution of PathogenicMicroorganisms · 2026Review
- Multidrug efflux pumps and innate azole resistance of Mucor lusitanicus.The Journal of antimicrobial chemotherapy · 2025Article
- Leveraging synthetic genetic array screening to identify therapeutic targets and inhibitors for combatting azole resistance inMicrobiology spectrum · 2025Article
- Understanding the mechanisms of resistance to azole antifungals inJAC-antimicrobial resistance · 2025Review
- Mechanisms of multidrug resistance caused by an Ipi1 mutation in the fungal pathogen Candida glabrata.Nature communications · 2025Article
- Dual inhibition of ERG11 and CDR2 in drug-resistantFrontiers in pharmacology · 2025Article
- Overlapping coactivator function is required for transcriptional activation by the Candida glabrata Pdr1 transcription factor.Genetics · 2024Article
- Review
- Parallel evolution of fluconazole resistance and tolerance inFrontiers in cellular and infection microbiology · 2024Article
- Recent gene selection and drug resistance underscore clinical adaptation across Candida species.Nature microbiology · 2024Article
- InJournal of fungi (Basel, Switzerland) · 2023Article
- UsingVirulence · 2022Article
- Genomic evolution towards azole resistance in Candida glabrata clinical isolates unveils the importance of CgHxt4/6/7 in azole accumulation.Communications biology · 2022Article
- Article
- Zn(II) and Cd(II) Complexes of AMT1/MAC1 Homologous Cys/His-Rich Domains: So Similar yet So Different.Inorganic chemistry · 2022Article
- Inositol Phosphoryl Transferase, Ipt1, Is a Critical Determinant of Azole Resistance and Virulence Phenotypes inJournal of fungi (Basel, Switzerland) · 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
- Article
- Antifungal properties of (2S, 4R)-Ketoconazole sulfonamide analogs.Frontiers in drug discovery · 2022Article
106 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The resistance mechanisms to azole antifungal agents were investigated in this study with two pairs of Candida glabrata clinical isolates recovered from two separate AIDS patients. The two pairs each contained a fluconazole-susceptible isolate and a fluconazole-resistant isolate, the latter with cross-resistance to itraconazole and ketoconazole. Since the accumulation of fluconazole and of another unrelated substance, rhodamine 6G, was reduced in the azole-resistant isolates, enhanced drug efflux was considered as a possible resistance mechanism. The expression of multidrug efflux transporter genes was therefore examined in the azole-susceptible and azole-resistant yeast isolates. For this purpose, C. glabrata genes conferring resistance to azole antifungals were cloned in a Saccharomyces cerevisiae strain in which the ATP binding cassette (ABC) transporter gene PDR5 was deleted. Three different genes were recovered, and among them, only C. glabrata CDR1 (CgCDR1), a gene similar to the Candida albicans ABC transporter CDR genes, was upregulated by a factor of 5 to 8 in the azole-resistant isolates. A correlation between upregulation of this gene and azole resistance was thus established. The deletion of CgCDR1 in an azole-resistant C. glabrata clinical isolate rendered the resulting mutant (DSY1041) susceptible to azole derivatives as the azole-susceptible clinical parent, thus providing genetic evidence that a specific mechanism was involved in the azole resistance of a clinical isolate. When CgCDR1 obtained from an azole-susceptible isolate was reintroduced with the help of a centromeric vector in DSY1041, azole resistance was restored and thus suggested that a trans-acting mutation(s) could be made responsible for the increased expression of this ABC transporter gene in the azole-resistant strain. This study demonstrates for the first time the determinant role of an ABC transporter gene in the acquisition of resistance to azole antifungals by C. glabrata clinical isolates.
Indexed as
Identifiers
What OpenQuestion holds
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.