Exposure of the yeast Candida albicans to the anti-neoplastic agent adriamycin increases the tolerance to amphotericin B.
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 24h 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.
O'Keeffe
Joseph
J
Medical Mycology Unit, National Institute for Cellular Biotechnology, Department of Biology, National University of Ireland, Maynooth, Co. Kildare, Ireland.
Doyle
Sean
S
Kavanagh
Kevin
K
D000666:Amphotericin B / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D004347:Drug Interactions; D004361:Drug Tolerance; D004875:Ergosterol / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D000935:Antifungal Agents; D000666:Amphotericin B; D004317:Doxorubicin; D004875:Ergosterol