TY - JOUR
T1 - Identification and functional characterization of Penicillium marneffei major facilitator superfamily (MFS) transporters
AU - Utami, Setyowati T.
AU - Indriani, Carissa I.
AU - Bowolaksono, Anom
AU - Yaguchi, Takashi
AU - Chen, Xinyue
AU - Niimi, Kyoko
AU - Niimi, Masakazu
AU - Kajiwara, Susumu
N1 - Funding Information:
We thank Astella Pharma Inc. for providing micafungin.
Publisher Copyright:
© 2020, © 2020 Japan Society for Bioscience, Biotechnology, and Agrochemistry.
PY - 2020/7/2
Y1 - 2020/7/2
N2 - 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.
AB - 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.
KW - DHA subfamily
KW - Major facilitator superfamily (MFS) transporter
KW - multidrug resistance
KW - rug efflux pump
KW - Saccharomyces cerevisiae
UR - http://www.scopus.com/inward/record.url?scp=85081366111&partnerID=8YFLogxK
U2 - 10.1080/09168451.2020.1732185
DO - 10.1080/09168451.2020.1732185
M3 - Article
C2 - 32163007
AN - SCOPUS:85081366111
SN - 0916-8451
VL - 84
SP - 1373
EP - 1383
JO - Bioscience, Biotechnology and Biochemistry
JF - Bioscience, Biotechnology and Biochemistry
IS - 7
ER -