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  • Title: Palmarumycin P3 Reverses Mrr1-Mediated Azole Resistance by Blocking the Efflux Pump Mdr1.
    Author: Song M, Zhang M, Lu J, Xie F, Song J, Luan X, Hou X, Lou H, Chang W.
    Journal: Antimicrob Agents Chemother; 2022 Mar 15; 66(3):e0212621. PubMed ID: 35041505.
    Abstract:
    Palmarumycin P3 (PP3) reduces fluconazole-induced MDR1 transcription to reverse azole resistance in clinical Candida strains. Here, we demonstrated that PP3 restores the susceptibility to several antifungal drugs for Candida albicans strains with gain-of-function mutations in the transcription factor Mrr1. In addition, PP3 inhibits the efflux of Mdr1 substrates by C. albicans strains harboring hyperactive MRR1 alleles. Molecular docking revealed that PP3 is a potential Mdr1 blocker that binds to the substrate binding pocket of Mdr1.
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