Palmarumycin P3 Reverses Mrr1-Mediated Azole Resistance by Blocking the Efflux Pump Mdr1.

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.

SUBMITTER: Song M 

PROVIDER: S-EPMC8923160 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature