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Aureobasidin A, an antifungal cyclic depsipeptide antibiotic, is a substrate for both human MDR1 and MDR2/P‐glycoproteins
Author(s) -
Kino Kouichi,
Taguchi Yoshitomo,
Yamada Kouji,
Komano Tohru,
Ueda Kazumitsu
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(96)01265-3
Subject(s) - p glycoprotein , multiple drug resistance , depsipeptide , atp binding cassette transporter , biology , efflux , transporter , saccharomyces cerevisiae , drug resistance , biochemistry , pharmacology , antibiotics , microbiology and biotechnology , yeast , gene
The human MDR1 gene encodes the multidrug transporter P‐glycoprotein (Pgp). Although the MDR2/Pgp shares about 80% identity at the amino acid level with the MDRI/Pgp, the MDR2/Pgp cannot act as a multidrug transporter. We examined the drug sensitivity of Saccharomyces cerevisiae expressing either the human MDR1/Pgp or MDR2/Pgp. The human MDR1/Pgp conferred about 4‐fold resistance to aureobasidin A, a cyclic depsipeptide antifungal antibiotic, on the drug‐sensitive yeast strains. Interestingly the human MDR2/Pgp also conferred about 2.5‐fold resistance to aureobasidin A. The resistance to aureobasidin A conferred by the MDR2/Pgp as well as by the MDR1/Pgp was overcome by vinblastine, verapamil, and cyclosporin A, depending on their concentrations, but not by colchicine. Aureobasidin A probably interacts directly with Pgps, because it overcame multidrug resistance of human cells and inhibited azidopine photoaffinity labeling of MDRI/Pgp in human cell membranes. These results suggest the possibility that the human MDR1 and MDR2/Pgps have conserved domain(s) for drug recognition.