ArticleAntimicrobial agents and chemotherapy2012
The monoamine oxidase A inhibitor clorgyline is a broad-spectrum inhibitor of fungal ABC and MFS transporter efflux pump activities which reverses the azole resistance of Candida albicans and Candida glabrata clinical isolates.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed.
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- Azole Combinations and Multi-Targeting Drugs That Synergistically InhibitJournal of fungi (Basel, Switzerland) · 2024Review
- Modulators of Candida albicans Membrane Drug Transporters: A Lucrative Portfolio for the Development of Effective Antifungals.Molecular biotechnology · 2024Review
- Repurposing a human acetyl-CoA carboxylase inhibitor firsocostat to treat fungal candidiasis alone and in combination.Antimicrobial agents and chemotherapy · 2024Article
- Azole potentiation in Candida species.PLoS pathogens · 2023Article
- Clorgyline Analogs Synergize with Azoles against Drug Efflux inJournal of fungi (Basel, Switzerland) · 2023Article
- Molecular Investigation of the Antitumor Effects of Monoamine Oxidase Inhibitors in Breast Cancer Cells.BioMed research international · 2023Article
- The fungal expel of 5-fluorocytosine derived fluoropyrimidines mitigates its antifungal activity and generates a cytotoxic environment.PLoS pathogens · 2022Article
- Extracts from Argentinian native plants reverse fluconazole resistance in Candida species by inhibiting the efflux transporters Mdr1 and Cdr1.BMC complementary medicine and therapies · 2022Article
- Antifungal Activity of Mexican Propolis on Clinical Isolates ofMolecules (Basel, Switzerland) · 2022Article
- Repurposing pantoprazole and haloperidol as efflux pump inhibitors in azole resistant clinicalSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- Inhibitor-Resistant Mutants Give Important Insights into Candida albicans ABC Transporter Cdr1 Substrate Specificity and Help Elucidate Efflux Pump Inhibition.Antimicrobial agents and chemotherapy · 2022Article
- Activity of antifungal drugs and Brazilian red and green propolis extracted with different methodologies against oral isolates of Candida spp.BMC complementary medicine and therapies · 2021Article
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7 authors.
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Abstract
Resistance to the commonly used azole antifungal fluconazole (FLC) can develop due to overexpression of ATP-binding cassette (ABC) and major facilitator superfamily (MFS) plasma membrane transporters. An approach to overcoming this resistance is to identify inhibitors of these efflux pumps. We have developed a pump assay suitable for high-throughput screening (HTS) that uses recombinant Saccharomyces cerevisiae strains hyperexpressing individual transporters from the opportunistic fungal pathogen Candida albicans. The recombinant strains possess greater resistance to azoles and other pump substrates than the parental host strain. A flow cytometry-based HTS, which measured increased intracellular retention of the fluorescent pump substrate rhodamine 6G (R6G) within yeast cells, was used to screen the Prestwick Chemical Library (PCL) of 1,200 marketed drugs. Nine compounds were identified as hits, and the monoamine oxidase A inhibitor (MAOI) clorgyline was identified as an inhibitor of two C. albicans ABC efflux pumps, CaCdr1p and CaCdr2p. Secondary in vitro assays confirmed inhibition of pump-mediated efflux by clorgyline. Clorgyline also reversed the FLC resistance of S. cerevisiae strains expressing other individual fungal ABC transporters (Candida glabrata Cdr1p or Candida krusei Abc1p) or the C. albicans MFS transporter Mdr1p. Recombinant strains were also chemosensitized by clorgyline to other azoles (itraconazole and miconazole). Importantly, clorgyline showed synergy with FLC against FLC-resistant C. albicans clinical isolates and a C. glabrata strain and inhibited R6G efflux from a FLC-resistant C. albicans clinical isolate. Clorgyline is a novel broad-spectrum inhibitor of two classes of fungal efflux pumps that acts synergistically with azoles against azole-resistant C. albicans and C. glabrata strains.
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