The activity of amphotericin B against Candida albicans is not directly associated with extracellular calcium concentration.
The ability of amphotericin B to increase intracellular calcium concentrations in human cells is associated with the toxicity of this antifungal agent. The present study was performed to determine whether amphotericin B affects the influx or efflux of calcium in Candida albicans, and whether the antifungal activity of amphotericin B is dependent upon extracellular calcium concentrations. Concentration-response studies demonstrated that the addition of up to 1 mM EGTA to standard growth medium, with a more than 4000-fold decrease in extracellular calcium concentration, had no effect on the activity of amphotericin B against C. albicans. Amphotericin B did affect the kinetics of calcium influx acutely (< or =10 min), but had no net effect on long-term (1-24 h) calcium accumulation. Calcium efflux was also not affected by amphotericin B. These results indicate that, unlike its effects on mammalian cells, the toxicity of amphotericin B against C. albicans is not dependent upon increased movement of calcium across the cell membrane or the presence of extracellular calcium.
Rogers
P David
PD
Department of Pharmacy Practice, Division of Infectious Diseases, University of Mississippi Medical Center, Jackson, MS 39216, USA. drogers@utmem.edu
Kramer
Robert E
RE
Crews
Janice K
JK
Lewis
Russell E
RE
D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D003470:Culture Media; D004533:Egtazic Acid / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D013936:Thymidine / Q000378:metabolism
D000935:Antifungal Agents; D002614:Chelating Agents; D003470:Culture Media; D004533:Egtazic Acid; D000666:Amphotericin B; D002118:Calcium; D013936:Thymidine