Human antimicrobial peptides' antifungal activity against Aspergillus fumigatus.
In light of the need for new antifungals, we compared the in vitro antifungal activity of two peptides derived from human lactoferrin (hLF), i.e., hLF(1-11) and hLF(21-31), two analogs of histatin 5, further referred to as dhvar4 and dhvar5, and two ubiquicidin (UBI)-derived peptides, i.e., UBI 18-35 and UBI 29-41, with that of amphotericin B against Aspergillus fumigatus hyphae using the MTT assay. The results revealed a dose-dependent antifungal activity for all peptides, with dhvar5 being the most potent peptide. In addition, hLF(1-11), dhvar5, and UBI 18-35 were effective against A. fumigatus conidia. Furthermore, hLF(1-11) did not lyze human erythrocytes, whereas dhvar5 (>or=16 microM) and UBI 18-35 (>or=20 microM) were hemolytic. Based on these in vitro results and their effectiveness against infections in mice, we concluded that hLF(1-11) and dhvar5 are promising candidates for the development of new agents against A. fumigatus infections.
Lupetti
A
A
Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands. alupetti@biomed.unipi.it
van Dissel
J T
JT
Brouwer
C P J M
CP
Nibbering
P H
PH
D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology* / Q000633:toxicity; D001228:Aspergillosis / Q000188:drug therapy; D001232:Aspergillus fumigatus / Q000187:drug effects*; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis; D006801:Humans; D025301:Hyphae / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D013194:Staining and Labeling; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D013778:Tetrazolium Salts; D013844:Thiazoles; D000666:Amphotericin B; C022616:thiazolyl blue