Adriamycin alters the expression of drug efflux pumps and confers amphotericin B tolerance in Candida albicans.
The aim of the work presented here was to establish whether exposure of the yeast C. albicans to adriamycin altered the expression of the CDR1 drug efflux pump and consequently altered the susceptibility of the yeast to amphotericin B. Using a monoclonal antibody directed against human MDR1 and polyclonal antibodies against CDR1 (Candida drug resistance), we demonstrated that adriamycin induces an elevation in the expression of the CDR1 efflux pump which, together with previously recorded alterations in the composition of the fungal cell membrane, may confer tolerance to amphotericin B. This work highlights the fact that adriamycin therapy may inadvertently alter the susceptibility of C. albicans to amphotericin B, which may have deleterious consequences for anti-cancer chemotherapy regimes incorporating this anti-neoplastic agent.
O'Keeffe
Joseph
J
Medical Mycology Unit, National Institute for Cellular Biotechnology, Department of Biology, NUI Maynooth, Co. Kildare, Ireland.
Kavanagh
Kevin
K
D000666:Amphotericin B / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D004317:Doxorubicin / Q000009:adverse effects*; D004347:Drug Interactions; D025141:Drug Resistance, Fungal; D005656:Fungal Proteins / Q000096:biosynthesis* / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000096:biosynthesis* / Q000378:metabolism; D008826:Microbial Sensitivity Tests
D000903:Antibiotics, Antineoplastic; D000935:Antifungal Agents; C094693:CDR1 protein, Candida albicans; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D000666:Amphotericin B; D004317:Doxorubicin