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Identification and functional characterization of Penicillium marneffei major facilitator superfamily (MFS) transporters.

Bioscience, biotechnology, and biochemistry (2020-03-13)
Setyowati T Utami, Carissa I Indriani, Anom Bowolaksono, Takashi Yaguchi, Xinyue Chen, Kyoko Niimi, Masakazu Niimi, Susumu Kajiwara
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Cerulenin, ≥98% (HPLC), from Cephalosporium caerulens
Sigma-Aldrich
红海海绵素A, from sea sponge, ≥85% (HPLC), waxy solid
Sigma-Aldrich
11-(1H-吡咯-1-基)十一烷-1-硫醇, 96%