Identification and functional characterization of Penicillium marneffei pleiotropic drug resistance transporters ABC1 and ABC2

© 2016, © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Penicilliosis caused by the dimorphic fungus Penicillium marneffei is an endemic,...

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Main Authors: Siribun Panapruksachat, Shun Iwatani, Takahiro Oura, Nongnuch Vanittanakom, Ariya Chindamporn, Kyoko Niimi, Masakazu Niimi, Erwin Lamping, Richard D. Cannon, Susumu Kajiwara
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Published: 2018
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/56121
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spelling th-cmuir.6653943832-561212018-09-05T03:09:15Z Identification and functional characterization of Penicillium marneffei pleiotropic drug resistance transporters ABC1 and ABC2 Siribun Panapruksachat Shun Iwatani Takahiro Oura Nongnuch Vanittanakom Ariya Chindamporn Kyoko Niimi Masakazu Niimi Erwin Lamping Richard D. Cannon Susumu Kajiwara Medicine © 2016, © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Penicilliosis caused by the dimorphic fungus Penicillium marneffei is an endemic, AIDS-defining illness and, after tuberculosis and cryptococcosis, the third most common opportunistic infection of AIDS patients in tropical Southeast Asia. Untreated, patients have poor prognosis; however, primary amphotericin B treatment followed by prolonged itraconazole prophylaxis is effective. To identify ATP-binding cassette (ABC) transporters that may play a role in potential multidrug resistance of P. marneffei, we identified and classified all 46 P. marneffei ABC transporters from the genome sequence. PmABC1 and PmABC2 were most similar to the archetype Candida albicans multidrug efflux pump gene CDR1. P. marneffei Abc1p (PmAbc1p) was functionally expressed in Saccharomyces cerevisiae, although at rather low levels, and correctly localized to the plasma membrane, causing cells to be fourfold to eightfold more resistant to azoles and many other xenobiotics than untransformed cells. P. marneffei Abc2p (PmAbc2p) was expressed at similarly low levels, but it had no efflux activity and did not properly localize to the plasma membrane. Interestingly, PmAbc1p mislocalized and lost its transport activity when cells were shifted to 37 °C. We conclude that expression of PmAbc1p in S. cerevisiae confers resistance to several xenobiotics indicating that PmAbc1p may be a multidrug efflux pump. 2018-09-05T03:09:15Z 2018-09-05T03:09:15Z 2016-07-01 Journal 14602709 13693786 2-s2.0-84981747418 10.1093/mmy/myv117 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84981747418&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/56121
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Medicine
spellingShingle Medicine
Siribun Panapruksachat
Shun Iwatani
Takahiro Oura
Nongnuch Vanittanakom
Ariya Chindamporn
Kyoko Niimi
Masakazu Niimi
Erwin Lamping
Richard D. Cannon
Susumu Kajiwara
Identification and functional characterization of Penicillium marneffei pleiotropic drug resistance transporters ABC1 and ABC2
description © 2016, © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Penicilliosis caused by the dimorphic fungus Penicillium marneffei is an endemic, AIDS-defining illness and, after tuberculosis and cryptococcosis, the third most common opportunistic infection of AIDS patients in tropical Southeast Asia. Untreated, patients have poor prognosis; however, primary amphotericin B treatment followed by prolonged itraconazole prophylaxis is effective. To identify ATP-binding cassette (ABC) transporters that may play a role in potential multidrug resistance of P. marneffei, we identified and classified all 46 P. marneffei ABC transporters from the genome sequence. PmABC1 and PmABC2 were most similar to the archetype Candida albicans multidrug efflux pump gene CDR1. P. marneffei Abc1p (PmAbc1p) was functionally expressed in Saccharomyces cerevisiae, although at rather low levels, and correctly localized to the plasma membrane, causing cells to be fourfold to eightfold more resistant to azoles and many other xenobiotics than untransformed cells. P. marneffei Abc2p (PmAbc2p) was expressed at similarly low levels, but it had no efflux activity and did not properly localize to the plasma membrane. Interestingly, PmAbc1p mislocalized and lost its transport activity when cells were shifted to 37 °C. We conclude that expression of PmAbc1p in S. cerevisiae confers resistance to several xenobiotics indicating that PmAbc1p may be a multidrug efflux pump.
format Journal
author Siribun Panapruksachat
Shun Iwatani
Takahiro Oura
Nongnuch Vanittanakom
Ariya Chindamporn
Kyoko Niimi
Masakazu Niimi
Erwin Lamping
Richard D. Cannon
Susumu Kajiwara
author_facet Siribun Panapruksachat
Shun Iwatani
Takahiro Oura
Nongnuch Vanittanakom
Ariya Chindamporn
Kyoko Niimi
Masakazu Niimi
Erwin Lamping
Richard D. Cannon
Susumu Kajiwara
author_sort Siribun Panapruksachat
title Identification and functional characterization of Penicillium marneffei pleiotropic drug resistance transporters ABC1 and ABC2
title_short Identification and functional characterization of Penicillium marneffei pleiotropic drug resistance transporters ABC1 and ABC2
title_full Identification and functional characterization of Penicillium marneffei pleiotropic drug resistance transporters ABC1 and ABC2
title_fullStr Identification and functional characterization of Penicillium marneffei pleiotropic drug resistance transporters ABC1 and ABC2
title_full_unstemmed Identification and functional characterization of Penicillium marneffei pleiotropic drug resistance transporters ABC1 and ABC2
title_sort identification and functional characterization of penicillium marneffei pleiotropic drug resistance transporters abc1 and abc2
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84981747418&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/56121
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