Human lactoferrin-derived peptide's antifungal activities against disseminated Candida albicans infection.

Abstract

BACKGROUND:

Because the human lactoferrin-derived peptide, hLF(1-11), exerts potent in vitro candidacidal activity, we investigated whether it displays antifungal activity against disseminated Candida albicans infections.

METHODS:

Neutropenic mice were intravenously infected with C. albicans and, 24 h later, were injected with hLF(1-11); 18 h later, the number of viable yeasts in the kidneys was determined microbiologically, the size and number of infectious foci were determined histologically, and serum cytokine levels were determined by immunoassays.

RESULTS:

hLF(1-11) was effective (maximum reduction, 1.5 logs) against disseminated C. albicans infections, and its antifungal activity leveled off at a concentration of 0.4 ng of hLF(1-11)/kg of body weight. The antifungal activity of hLF(1-11) was increased in mice injected with interleukin (IL)-10 neutralizing antibodies, which suggests that IL-10 reduces the antifungal activity of hLF(1-11). In agreement with this result was the finding that injection of high doses of hLF(1-11) into infected mice was accompanied by increased levels of IL-10 in serum. Microscopic analysis revealed that infectious foci in kidneys of hLF(1-11)-treated mice contained mainly blastoconidia, whereas filamentous forms were abundant in untreated mice. The peptide inhibited the in vitro morphological transition of C. albicans, in a dose-dependent manner. : hLF(1-11) is effective against disseminated C. albicans infections; and its effects on C. albicans viability and virulence and on host cells may explain this antifungal activity.

• Authors: Antonella Lupetti, Carlo P J M Brouwer, Sylvia J P Bogaards, Mick M Welling, Emile de Heer, Mario Campa, Jaap T van Dissel, Robert H E Friesen, Peter H Nibbering
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 196 Issue 9 Pg. 1416-24 (Nov 01 2007) ISSN: 0022-1899 [Print] United States
• PMID: 17922408 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antifungal Agents
• Carrier Proteins
• LTF protein, human
• Interleukin-10
• Fluconazole
• Lactoferrin

Topics

• Animals
• Antifungal Agents (pharmacology)
• Candida albicans (drug effects)
• Candidiasis (drug therapy, microbiology)
• Carrier Proteins (pharmacology)
• Dose-Response Relationship, Drug
• Drug Resistance, Fungal
• Female
• Fluconazole (pharmacology)
• Humans
• Interleukin-10 (blood)
• Kidney Diseases (drug therapy, microbiology, pathology)
• Lactoferrin
• Mice
• Neutropenia
• Specific Pathogen-Free Organisms