UK-2A, B, C, and D, Novel Antifungal Antibiotics from Streptomyces sp. 517-02. VII. Membrane Injury Induced by C9-UK-2A, a Derivative of UK-2A, in Rhodotorula mucilaginosa IFO 0001.
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- TANI KAZUNORI
- Graduate School of Science, Osaka City University
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- USUKI YOSHINOSUKE
- Graduate School of Science, Osaka City University
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- MOTOBA KAZUHIKO
- Graduate School of Science, Osaka City University
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- FUJITA KEN-ICHI
- Graduate School of Science, Osaka City University
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- TANIGUCHI MAKOTO
- Graduate School of Science, Osaka City University
書誌事項
- タイトル別名
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- VII. Membrane Injury Induced by C9-UK-2A, a Derivative of UK-2A, in <i>Rhodotorula mucilaginosa</i> IFO 0001
この論文をさがす
説明
UK-2A is a potent antifungal antibiotic and its structure is highly similar to that of antimycin A3 (AA). UK-2A and AA inhibit mitochondrial electron transport at complex III. However, the antifungal activities of UK-2A and AA disappear after 48-hour treatment. In an attempt to improve the duration of the antifungal activity of UK-2A, several UK-2A derivatives were prepared by substituting its nine-membered dilactone ring with an n-alkyl or an isoprenyl moiety. Among all the derivatives tested, C9- and C10-UK-2A showed the most potent and durable antifungal activities against a strict aerobic yeast, Rhodotorula mucilaginosa IFO 0001. C9-UK-2A, in particular, continued to demonstrate its broad-spectrum antifungal activity after 120-hour treatment. Therefore, we focused on C9-UK-2A to further examine its mode of action against the yeast. Interestingly, C9-UK-2A did not inhibit cellular respiration of the cells even at concentrations greater than 100μg/ml. C9-UK-2A gradually induced the efflux of potassium ions from the cells. Moreover, C9-UK-2A gradually induced the release of glucose from glucose-encapsulating liposomes. The patterns of efflux and release induced by C9-UK-2A were not as rapid as those seen with amphotericin B. These results suggest a membrane injury caused by C9-UK-2A in R. mucilaginosa IFO 0001.
収録刊行物
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- The Journal of Antibiotics
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The Journal of Antibiotics 55 (3), 315-321, 2002
公益財団法人 日本感染症医薬品協会