ArticlePLoS pathogens2010
Azole drugs are imported by facilitated diffusion in Candida albicans and other pathogenic fungi.
Article in PLoS pathogens, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 112 citations in OpenAlex.
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- Suppressed Protein Translation Caused by MSP-8 Deficiency Determines Fungal Multidrug Resistance with Fitness Cost.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Azole resistance in Aspergillus fumigatus- comprehensive review.Archives of microbiology · 2024Review
- Increased Absorption and Inhibitory Activity againstMicroorganisms · 2023Article
- Is theMicroorganisms · 2023Article
- Transport Across Membranes: Techniques for Measuring Drug Import in Fungal Cells.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Genomic evolution towards azole resistance in Candida glabrata clinical isolates unveils the importance of CgHxt4/6/7 in azole accumulation.Communications biology · 2022Article
- 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
- A Chemogenomic Toolkit to Evaluate the "Ins and Outs" of Yeast Plasma Membrane Transporters.mBio · 2022Article
- Inositol Phosphoryl Transferase, Ipt1, Is a Critical Determinant of Azole Resistance and Virulence Phenotypes inJournal of fungi (Basel, Switzerland) · 2022Article
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- Cell Wall Proteome Profiling of aMicroorganisms · 2021Article
- Combining Colistin and Fluconazole Synergistically Increases Fungal Membrane Permeability and Antifungal Cidality.ACS infectious diseases · 2021Article
- Transcriptome Signatures Predict Phenotypic Variations ofFrontiers in cellular and infection microbiology · 2021Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Despite the wealth of knowledge regarding the mechanisms of action and the mechanisms of resistance to azole antifungals, very little is known about how the azoles are imported into pathogenic fungal cells. Here the in-vitro accumulation and import of Fluconazole (FLC) was examined in the pathogenic fungus, Candida albicans. In energized cells, FLC accumulation correlates inversely with expression of ATP-dependent efflux pumps. In de-energized cells, all strains accumulate FLC, suggesting that FLC import is not ATP-dependent. The kinetics of import in de-energized cells displays saturation kinetics with a K(m) of 0.64 μM and V(max) of 0.0056 pmol/min/10⁸ cells, demonstrating that FLC import proceeds via facilitated diffusion through a transporter rather than passive diffusion. Other azoles inhibit FLC import on a mole/mole basis, suggesting that all azoles utilize the same facilitated diffusion mechanism. An analysis of related compounds indicates that competition for azole import depends on an aromatic ring and an imidazole or triazole ring together in one molecule. Import of FLC by facilitated diffusion is observed in other fungi, including Cryptococcus neoformans, Saccharomyces cerevisiae, and Candida krusei, indicating that the mechanism of transport is conserved among fungal species. FLC import was shown to vary among Candida albicans resistant clinical isolates, suggesting that altered facilitated diffusion may be a previously uncharacterized mechanism of resistance to azole drugs.
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