ArticleThe Journal of antimicrobial chemotherapy2015
Identification and properties of plasma membrane azole efflux pumps from the pathogenic fungi Cryptococcus gattii and Cryptococcus neoformans.
Article in The Journal of antimicrobial chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
- Dynamics associated with the efflux pumps in biofilms and persister cells ofMicrobiology spectrum · 2026Article
- Multidrug efflux pumps and innate azole resistance of Mucor lusitanicus.The Journal of antimicrobial chemotherapy · 2025Article
- Uncovering the antifungal potential of Cannabidiol and Cannabidivarin.PLoS neglected tropical diseases · 2025Article
- Induction of pan-azole resistance inFrontiers in cellular and infection microbiology · 2025Article
- Fluconazole Resistance and Heteroresistance in Cryptococcus spp.: Mechanisms and Implications.Revista da Sociedade Brasileira de Medicina Tropical · 2025Review
- Article
- Synergistic effect of the verapamil and amphotericin B against Cryptococcus neoformans.Folia microbiologica · 2023Article
- The Microevolution of Antifungal Drug Resistance in Pathogenic Fungi.Microorganisms · 2023Review
- Involvement of AoMdr1 in the Regulation of the Fluconazole Resistance, Mycelial Fusion, Conidiation, and Trap Formation ofMicroorganisms · 2023Article
- Organoselenium Has a Potent Fungicidal Effect on Cryptococcus neoformans and Inhibits the Virulence Factors.Antimicrobial agents and chemotherapy · 2023Article
- Combating increased antifungal drug resistance inActa biochimica et biophysica Sinica · 2023Review
- Article
- Gene expression profiles of ERG11, MDR1 and AFR1 in Cryptococcus neoformans var.grubbi from HIV patientsBiomedica : revista del Instituto Nacional de Salud · 2022Article
- Molecular mechanisms of acquired antifungal drug resistance in principal fungal pathogens and EUCAST guidance for their laboratory detection and clinical implications.The Journal of antimicrobial chemotherapy · 2022Review
- Novel ABC Transporter Associated with Fluconazole Resistance in Aging ofJournal of fungi (Basel, Switzerland) · 2022Article
- Lack of Association between Fluconazole Susceptibility andJournal of fungi (Basel, Switzerland) · 2022Article
- Fungicide effects on human fungal pathogens: Cross-resistance to medical drugs and beyond.PLoS pathogens · 2021Review
- The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin.Drugs · 2021Review
- Low Glucose Mediated Fluconazole Tolerance inJournal of fungi (Basel, Switzerland) · 2021Article
- The Environmental Effects on Virulence Factors and the Antifungal Susceptibility ofInternational journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
objectivesCryptococcus gattii from the North American Northwest (NW) have higher azole MICs than do non-NW C. gattii or Cryptococcus neoformans. Since mechanisms of azole resistance in C. gattii are not known, we identified C. gattii and C. neoformans plasma membrane azole efflux pumps and characterized their properties.
methodsThe C. gattii R265 genome was searched for orthologues of known fungal azole efflux genes, expression of candidate genes was assessed by RT-PCR and the expressed genes' cDNAs were cloned and expressed in Saccharomyces cerevisiae. Azole MICs and intracellular [(3)H]fluconazole were measured in C. gattii and C. neoformans and in S. cerevisiae expressing each cDNA of interest, as was [(3)H]fluconazole uptake by post-Golgi vesicles (PGVs) isolated from S. cerevisiae sec6-4 mutants expressing each cDNA of interest.
resultsIntracellular [(3)H]fluconazole concentrations were inversely correlated with fluconazole MICs only in 25 NW C. gattii strains. S. cerevisiae expressing three C. gattii cDNAs (encoded by orthologues of C. neoformans AFR1 and MDR1 and the previously unstudied gene AFR2) and their C. neoformans counterparts had higher azole MICs and lower intracellular [(3)H]fluconazole concentrations than did empty-vector controls. PGVs from S. cerevisiae expressing all six Cryptococcus cDNAs also accumulated more [(3)H]fluconazole than did controls, and [(3)H]fluconazole transport by all six transporters of interest was ATP dependent and was inhibited by excess unlabelled fluconazole, voriconazole, itraconazole and posaconazole.
conclusionsWe conclude that C. gattii and C. neoformans AFR1, MDR1 and AFR2 encode ABC transporters that pump multiple azoles out of S. cerevisiae cells, thereby causing azole resistance.
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