ArticleAntimicrobial agents and chemotherapy2008
Synergistic effect of calcineurin inhibitors and fluconazole against Candida albicans biofilms.
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 117 papers.
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Who cites it
117 citing papers in PubMed, 230 citations in OpenAlex.
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- Fragmented but functional: Post-dispersion dynamics and phenotypic variation in dispersed biofilm-associated cells.Biofilm · 2026Article
- A Calcineurin Inhibitor as an Enhancer ofACS omega · 2026Article
- Antifungal effects and potential mechanism of bortezomib in combination with fluconazole againstFrontiers in cellular and infection microbiology · 2026Article
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- Targeting calcineurin: a synergistic strategy with caspofungin to induce farnesol-mediated quorum sensing in Nakaseomyces glabrata-an inoculum-dependent tale.The Biochemical journal · 2025Article
- Calcium transport systems as virulence determinants: Mechanistic insights into fungal pathogenicity and antifungal resistance.Virulence · 2025Review
- The calcineurin pathway regulates extreme thermotolerance, cell membrane and wall integrity, antifungal resistance, and virulence in Candida auris.PLoS pathogens · 2025Article
- In Vitro Assessment of Fluconazole and Cyclosporine A Antifungal Activities: A Promising Drug Combination Against DifferentJournal of fungi (Basel, Switzerland) · 2025Article
- Combinations of posaconazole and tacrolimus are effective against infections with azole-resistantFrontiers in cellular and infection microbiology · 2025Article
- Calcineurin activity in Fonsecaea pedrosoi: tacrolimus and cyclosporine A inhibited conidia growth, filamentation and showed synergism with itraconazole.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2024Article
- Evolutionary diversity of the control of the azole response by Tra1 across yeast species.G3 (Bethesda, Md.) · 2024Article
- Old and new strategies in therapy and diagnosis against fungal infections.Applied microbiology and biotechnology · 2024Review
- Synergistic Effect of Plant Compounds in Combination with Conventional Antimicrobials against Biofilm ofPharmaceuticals (Basel, Switzerland) · 2023Review
- Azole potentiation in Candida species.PLoS pathogens · 2023Article
- Antifungal drug-resistance mechanisms in Candida biofilms.Current opinion in microbiology · 2023Review
- Molecular dissection studies ofFrontiers in microbiology · 2023Article
57 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Calcineurin is a Ca2+-calmodulin-activated serine/threonine-specific protein phosphatase that governs multiple aspects of fungal physiology, including cation homeostasis, morphogenesis, antifungal drug susceptibility, and virulence. Growth of Candida albicans planktonic cells is sensitive to the calcineurin inhibitors FK506 and cyclosporine A (CsA) in combination with the azole antifungal fluconazole. This drug synergism is attributable to two effects: first, calcineurin inhibitors render fluconazole fungicidal rather than simply fungistatic, and second, membrane perturbation by azole inhibition of ergosterol biosynthesis increases intracellular calcineurin inhibitor concentrations. C. albicans cells in biofilms are up to 1,000-fold more resistant to fluconazole than planktonic cells. In both in vitro experiments and in an in vivo rat catheter model, C. albicans cells in biofilms were resistant to individually delivered fluconazole or calcineurin inhibitors but exquisitely sensitive to the combination of FK506-fluconazole or CsA-fluconazole. C. albicans strains lacking FKBP12 or expressing a dominant FK506-resistant calcineurin mutant subunit (Cnb1-1) formed biofilms that were resistant to FK506-fluconazole but susceptible to CsA-fluconazole, demonstrating that drug synergism is mediated via direct calcineurin inhibition. These findings reveal that calcineurin contributes to fluconazole resistance of biofilms and provide evidence that synergistic drug combinations may prove efficacious as novel therapeutic interventions to treat or prevent biofilms.
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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.