JAC Advance Access originally published online on January 6, 2003
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Journal of Antimicrobial Chemotherapy (2003) 51, 305-312
© 2003 The British Society for Antimicrobial Chemotherapy
The activity of amphotericin B against Candida albicans is not directly associated with extracellular calcium concentration
1 Department of Pharmacy Practice, Division of Infectious Diseases; 2 Department of Medicine; 3 Department of Microbiology; 4 Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216; 5 Department of Clinical Sciences and Administration, University of Houston College of Pharmacy, Houston, TX 77030, USA
Received 12 August 2002; returned 22 September 2002; revised 29 October 2002; accepted 4 November 2002
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. Concentrationresponse 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 (
10 min), but had no net effect on long-term (124 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.
Keywords: amphotericin B, Candida albicans, calcium
* Correspondence address. Suite 513, Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA. Tel: +1-901-448-3719; Fax: +1-901-448-1741; E-mail: drogers{at}utmem.edu