Exposure of the yeast Candida albicans to the anti‐neoplastic agent adriamycin increases the tolerance to amphotericin B

Exposure of the yeast Candida albicans to the anti‐neoplastic agent adriamycin increases the tolerance to amphotericin B
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DOI:
10.1211/0022357022359
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发表时间:
2003-12
影响因子:
3.3
通讯作者:
Joseph O'Keeffe;S. Doyle;K. Kavanagh
Joseph O'Keeffe;S. Doyle;K. Kavanagh
中科院分区:
医学3区
文献类型:
--
作者:
Joseph O'Keeffe;S. Doyle;K. Kavanagh

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癌症患者由于其免疫抑制状况而经历真菌感染的高发病率。这项工作研究了抗肿瘤药物阿霉素(阿霉素)与酵母菌白色念珠菌的相互作用,并检查了这种药物是否改变了酵母菌对阿替霉素B(一种用于治疗癌症患者全身真菌感染的抗真菌药物)的敏感性。阿霉素作用24 h后,C.白念珠菌,并增加了耐受性阿替霉素B的一个小的,但统计学上显着的程度。在添加阿霉素的培养基中生长抑制了C.白色念珠菌,这导致真菌细胞膜的麦角固醇含量降低。暴露于阿霉素48 h后,对阿替霉素B的耐受性丧失,这与真菌细胞膜的呼吸速率和麦角固醇含量的恢复一致。这项工作表明,短期暴露于阿霉素(24小时)增加了C。白念珠菌对阿霉素B的耐受性,这可能是由于阿霉素诱导氧化磷酸化破坏导致麦角甾醇含量降低而介导的。
Cancer patients experience a high incidence of fungal infections due to their immuno‐suppressed condition. This work has investigated the interaction of an anti‐neoplastic agent, adriamycin (doxorubicin), with the yeast Candida albicans and examined whether this drug altered the susceptibility of the yeast to amphotericin B – an anti‐fungal agent used for the treatment of systemic fungal infections in cancer patients. Exposure to adriamycin for 24 h increased the growth of C. albicans and increased the tolerance to amphotericin B by a small, but statistically significant, extent. Growth in adriamycin‐supplemented medium suppressed the respiration rate of C. albicans, which resulted in a decrease in the ergosterol content of the fungal cell membrane. The tolerance to amphotericin B was lost after exposure to adriamycin for 48 h, which coincided with a restoration in the respiration rate and the ergosterol content of the fungal cell membrane. This work demonstrated that short‐term exposure (24 h) to adriamycin increased the tolerance of C. albicans for amphotericin B, which may be mediated by a decrease in the ergosterol content as a result of an adriamycin‐induced disruption of oxidative phosphorylation.