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.
Modulation of In Vitro Fungicidal Activity of Human Lactoferrin against Candida albicans by Extracellular Cation Concentration and Target Cell Metabolic Activity
Mónica Viejo-Díaz,1,2 María T. Andrés,2 and José F. Fierro1,2*
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.
* Corresponding author. Mailing address: Department of Functional Biology (Microbiology), Faculty of Medicine, University of Oviedo, C/ Julian Claveria, 6, 33006 Oviedo, Spain. Phone: 34-985-103643. Fax: 34-985-103533. E-mail: jffierro{at}uniovi.es.
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.
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Copyright © 2004 by the American Society for Microbiology. All rights reserved.