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1 November 2007

Volume 196, Number 9
The Journal of Infectious Diseases 2007;196:1416–1424
© 2007 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2007/19609-0022$15.00
DOI: 10.1086/522427
MAJOR ARTICLE

Human Lactoferrin‐Derived Peptide's Antifungal Activities against Disseminated Candida albicans Infection

Antonella Lupetti,1,5,a

Carlo P. J. M. Brouwer,4,a

Sylvia J. P. Bogaards,1,4

Mick M. Welling,2

Emile de Heer,3

Mario Campa,5

Jaap T. van Dissel,1

Robert H. E. Friesen,4,b and

Peter H. Nibbering1

1Department of Infectious Diseases, 2Department of Radiology, Division of Nuclear Medicine, and 3Department of Pathology, Leiden University Medical Center, Leiden, and 4AM‐Pharma, Netherlands; 5Dipartimento di Patologia Sperimentale, Biotecnologie Mediche, Infettivologia ed Epidemiologia, Università di Pisa, Pisa, Italy

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

Conclusions.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.

Received 16 August 2006; accepted 16 April 2007; electronically published 2 October 2007.

Reprints or correspondence: Dr. Peter H. Nibbering, Dept. of Infectious Diseases, C5‐P, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands ().

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  • Potential conflicts of interest: none reported.

    Presented in part: 33rd National Meeting of the Italian Society of Microbiology, Naples, Italy, 16–19 October 2005; 7th International Conference on Lactoferrin: Structure, Function and Applications, Honolulu, Hawaii, 16–19 October 2005; 45th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, 16–19 December 2005; 29th European Peptide Symposium, Gdansk, Poland, 3–8 September 2006.

    Financial support: SenterNovem (contract ISO 44096 to R.H.E.F. and P.H.N.); Italian “Ministerio dell’Istruzione, dell’Universia e della Ricerca” (contract 2003062784 to A.L.).

  • A.L. and C.P.J.M.B. contributed equally to this study.

  • Present affiliation: Morphosys AG, Martinsried/Planegg, Germany.

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