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Modulation of In Vitro Fungicidal Activity of Human Lactoferrin against Candida albicans by Extracellular Cation Concentration and Target Cell Metabolic Activity

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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