Disruption of mitochondrial function in Candida albicans leads to reduced cellular ergosterol levels and elevated growth in the presence of amphotericin B.
A respiratory-deficient mutant of Candida albicans MEN was generated by culturing cells in medium supplemented with ethidium bromide at 37 degrees C for 5 days. The respiratory-deficient mutant (C. albicans MMU11) was incapable of growth on glycerol, had a reduced oxygen uptake rate and demonstrated an altered mitochondrial cytochrome profile. Respiratory-competent cybrids were formed by mitochondrial transfer following fusion of protoplasts with those of C. albicans ATCC 44990. Mutant MMU11 possessed lower levels of ergosterol than the parental isolates and the cybrids, and demonstrated a small but statistically significant increase in tolerance to amphotericin B. The results demonstrated that disruption of mitochondrial function in C. albicans increases the tolerance to amphotericin B, possibly mediated by a reduction in cellular ergosterol content.
Geraghty
Patrick
P
Medical Myology Unit, National Institute for Cellular Biotechnology, National University of Ireland Maynooth, Department of Biology, Co. Kildare, Ireland.
Kavanagh
Kevin
K
D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism; D025141:Drug Resistance, Fungal; D004875:Ergosterol / Q000032:analysis / Q000378:metabolism*; D004996:Ethidium; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009154:Mutation; D010101:Oxygen Consumption; D011523:Protoplasts / Q000378:metabolism
D000935:Antifungal Agents; D003580:Cytochromes; D024101:Mitochondrial Proteins; D000666:Amphotericin B; D004996:Ethidium; D004875:Ergosterol