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Unexpected effects of azole transporter inhibitors on antifungal susceptibility in Candida glabrata and other pathogenic Candida species
http://hdl.handle.net/10069/38282
http://hdl.handle.net/10069/38282ebbe5d65-5111-4af5-ba18-055f159b4824
名前 / ファイル | ライセンス | アクション |
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ISYK1027_Nagayoshi.pdf (1.7 MB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2018-06-07 | |||||
タイトル | ||||||
タイトル | Unexpected effects of azole transporter inhibitors on antifungal susceptibility in Candida glabrata and other pathogenic Candida species | |||||
言語 | en | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
資源タイプ | doctoral thesis | |||||
アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
著者 |
永吉, 洋介
× 永吉, 洋介 |
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著者別名 | ||||||
識別子Scheme | WEKO | |||||
識別子 | 116026 | |||||
姓名 | Nagayoshi, Yohsuke | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | The pathogenic fungus Candida glabrata is often resistant to azole antifungal agents. Drug efflux through azole transporters, such as Cdr1 and Cdr2, is a key mechanism of azole resistance and these genes are under the control of the transcription factor Pdr1. Recently, the monoamine oxidase A (MAO-A) inhibitor clorgyline was shown to inhibit the azole efflux pumps, leading to increased azole susceptibility in C. glabrata. In the present study, we have evaluated the effects of clorgyline on susceptibility of C. glabrata to not only azoles, but also to micafungin and amphotericin B, using wild-type and several mutant strains. The addition of clorgyline to the culture media increased fluconazole susceptibility of a C. glabrata wild-type strain, whereas micafungin and amphotericin B susceptibilities were markedly decreased. These phenomena were also observed in other medically important Candida species, including Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida krusei. Expression levels of CDR1, CDR2 and PDR1 mRNAs and an amount of Cdr1 protein in the C. glabrata wild-type strain were highly increased in response to the treatment with clorgyline. However, loss of Cdr1, Cdr2, Pdr1, and a putative clorgyline target (Fms1), which is an ortholog of human MAO-A, or overexpression of CDR1 did not affect the decreased susceptibility to micafungin and amphotericin B in the presence of clorgyline. The presence of other azole efflux pump inhibitors including milbemycin A4 oxime and carbonyl cyanide 3-chlorophenylhydrazone also decreased micafungin susceptibility in C. glabrata wild-type, Δcdr1, Δcdr2, and Δpdr1 strains. These findings suggest that azole efflux pump inhibitors increase azole susceptibility but concurrently induce decreased susceptibility to other classes of antifungals independent of azole transporter functions. | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 長崎大学学位論文 学位記番号:博(医歯薬)甲第1027号 学位授与年月日:平成30年3月7日 | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Author: Yohsuke Nagayoshi, Taiga Miyazaki, Shintaro Shimamura, Hironobu Nakayama, Asuka Minematsu, Shunsuke Yamauchi, Takahiro Takazono, Shigeki Nakamura, Katsunori Yanagihara, Shigeru Kohno, Hiroshi Mukae, Koichi Izumikawa | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Citation: PLoS ONE, 12(7), e0180990; 2017 | |||||
書誌情報 |
PLoS ONE 巻 12, 号 7, p. e0180990, 発行日 2018-03-07 |
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EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 19326203 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1371/journal.pone.0180990 | |||||
権利 | ||||||
権利情報 | c 2017 Nagayoshi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
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著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
その他のタイトル | ||||||
その他のタイトル | Candida glabrata およびその他のCandida属の抗真菌薬感受性におけるアゾールトランスポーター阻害薬の効果 | |||||
出版者 | ||||||
出版者 | Public Library of Science | |||||
関係URI | ||||||
識別子タイプ | HDL | |||||
関連識別子 | http://hdl.handle.net/10069/38069 | |||||
学位名 | ||||||
学位名 | 博士(医学) | |||||
学位授与機関 | ||||||
学位授与機関識別子Scheme | kakenhi | |||||
学位授与機関識別子 | 17301 | |||||
学位授与機関名 | Nagasaki University (長崎大学) | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2018-03-07 | |||||
学位授与番号 | ||||||
学位授与番号 | 甲医歯薬第1027号 | |||||
学位の種類 | ||||||
値 | 課程博士 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Nagasaki University (長崎大学), 博士(医学) (2018-03-07) |