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Antimicrobial Agents and Chemotherapy, April 2004, p. 1242-1248, Vol. 48, No. 4
0066-4804/04/$08.00+0 DOI: 10.1128/AAC.48.4.1242-1248.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Department of Functional Biology (Microbiology), Faculty of Medicine,1 Laboratory of Oral Microbiology, School of Stomatology, University of Oviedo, 33006 Oviedo, Spain2
Received 27 May 2003/ Returned for modification 9 December 2003/ Accepted 15 December 2003
The anti-Candida activity of the innate defense protein human lactoferrin was investigated. Lactoferrin displayed a clear fungicidal effect against Candida albicans only under low-strength conditions. This candidacidal activity was inversely correlated with the extracellular concentration of the monovalent cations and was prevented by Na+ and K+ (
30 mM) and by divalent cations (Ca2+ and Mg2+ at
4 mM). A slight cellular release of K+, cytosolic acidification, and a change in the membrane potential were observed in C. albicans cells treated with lactoferrin, suggesting that this protein directly or indirectly interacts with the cytoplasmic membrane. Mitochondrial inhibitors (carbonyl cyanide m-chlorophenylhydrazone, 2,4-dinitrophenol, azide, and antimycin) as well as anaerobic conditions significantly reduced the killing effect of lactoferrin. These results suggest that low-strength conditions and the cellular metabolic state may modulate the candidacidal activity of human lactoferrin.
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