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  • Title: Inhibition of fungal ABC transporters by unnarmicin A and unnarmicin C, novel cyclic peptides from marine bacterium.
    Author: Tanabe K, Lamping E, Adachi K, Takano Y, Kawabata K, Shizuri Y, Niimi M, Uehara Y.
    Journal: Biochem Biophys Res Commun; 2007 Dec 28; 364(4):990-5. PubMed ID: 17967417.
    Abstract:
    Novel inhibitors of fungal ATP-binding cassette transporters were obtained by screening compounds and crude extracts from marine-derived fungi and bacteria using disk diffusion assays of Saccharomyces cerevisiae strains overexpressing a variety of fungal multi-drug efflux pumps. The cyclodepsipeptides unnarmicin A and unnarmicin C were able to sensitize cells overexpressing azole drug pumps ScPdr5p, CaCdr1p, CgCdr1p, and CgPdh1p to sub-MIC concentrations of fluconazole without affecting the growth of CaCdr2p and CaMdr1p overexpressing cells. Unnarmicin A and unnarmicin C were potent inhibitors of rhodamine 6G efflux of CaCdr1p expressing cells with IC50 values of 3.61 and 5.65 microM, respectively. They inhibited the in vitro CaCdr1p ATPase activity at IC50 values of 0.495 and 0.688 microM, respectively. And most importantly, they were able to sensitize azole-resistant Candida albicans clinical isolates to fluconazole. Unnarmicin A and unnarmicin C are candidate efflux pump inhibitors with the potential to be used as adjuvants for antifungal chemotherapy.
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