Identification and functional characterization of Penicillium marneffei major facilitator superfamily (MFS) transporters |
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| Authors: | Setyowati T. Utami Carissa I. Indriani Anom Bowolaksono Takashi Yaguchi Xinyue Chen Kyoko Niimi |
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| Affiliation: | 1. School of Life Science and Technology, Tokyo Institute of Technology , Tokyo, Japan;2. School of Life Science and Technology, Tokyo Institute of Technology , Tokyo, Japan;3. Department of Biology School of Mathematics and Natural Sciences, Universitas Indonesia , Depok, Indonesia;4. Medical Mycology Research Center, Chiba University , Chiba, Japan |
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| Abstract: | ABSTRACT Penicillium marneffei is a thermally dimorphic fungus that causes penicilliosis, and become the third-most-common opportunistic fungal infection in immunocompromised patients in Southeast Asia. Azoles and amphotericin B have been introduced for the treatment, however, it is important to investigate possible mechanisms of azole resistance for future treatment failure. We identified 177 putative MFS transporters and classified into 17 subfamilies. Among those, members of the Drug:H+ antiporter 1 subfamily are known to confer resistance to antifungals. Out of 39 paralogs, three (encoded by PmMDR1, PmMDR2, and PmMDR3) were heterologously overexpressed in S. cerevisiae AD? conferred resistance to various drugs and compounds including azoles, albeit to different degrees. PmMDR1-expressing strain showed resistance to the broadest range of drugs, followed by the PmMDR3, and PmMDR2 conferred weak resistance to a limited range of drugs. We conclude that PmMDR1 and PmMDR3, may be able to serve as multidrug efflux pumps. |
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| Keywords: | Major facilitator superfamily (MFS) transporter DHA subfamily multidrug resistance rug efflux pump Saccharomyces cerevisiae |
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