Modulation of in vitro fungicidal activity of human lactoferrin against Candida albicans by extracellular cation concentration and target cell metabolic activity.
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(+) (> or 30 mM) and by divalent cations (Ca(2+) and Mg(2+) at > or 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.
Viejo-Díaz
Mónica
M
Department of Functional Biology (Microbiology), Faculty of Medicine, University of Oviedo, 33006 Oviedo, Spain.
Andrés
María T
MT
Fierro
José F
JF
D000935:Antifungal Agents / Q000494:pharmacology*; D000963:Antimetabolites / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism*; D002412:Cations / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007781:Lactoferrin / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011188:Potassium / Q000378:metabolism; D013104:Spheroplasts / Q000187:drug effects; D013696:Temperature
D000935:Antifungal Agents; D000963:Antimetabolites; D002412:Cations; D007781:Lactoferrin; D011188:Potassium