A critical comparison of the hemolytic and fungicidal activities of cationic antimicrobial peptides.
The hemolytic and fungicidal activity of a number of cationic antimicrobial peptides was investigated. Histatins and magainins were inactive against human erythrocytes and Candida albicans cells in phosphate buffered saline, but displayed strong activity against both cell types when tested in 1 mM potassium phosphate buffer supplemented with 287 mM glucose. The HC50/IC50 ratio, indicative of the therapeutic index, was about 30 for all peptides tested. PGLa was most hemolytic (HC50 = 0.6 microM) and had the lowest therapeutic index (HC50/IC50 = 0.5). Susceptibility to hemolysis was shown to increase with storage duration of the erythrocytes and also significant differences were found between blood collected from different individuals. In this report, a sensitive assay is proposed for the testing of the hemolytic activities of cationic peptides. This assay detects subtle differences between peptides and allows the comparison between the hemolytic and fungicidal potency of cationic peptides.
Helmerhorst
E J
EJ
Academic Centre for Dentistry Amsterdam (ACTA), Department of Oral Biochemistry, Vrije Universiteit, The Netherlands. ej.helmerhorst.obc.acta@med.vu.nl
Reijnders
I M
IM
van 't Hof
W
W
Veerman
E C
EC
Nieuw Amerongen
A V
AV
D000595:Amino Acid Sequence; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D002176:Candida albicans / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D006460:Hemolysin Proteins / Q000494:pharmacology*; D006461:Hemolysis; D054808:Histatins; D006801:Humans; D054806:Magainins; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D012471:Salivary Proteins and Peptides / Q000494:pharmacology*; D029867:Xenopus Proteins
D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; C068075:HTN3 protein, human; D006460:Hemolysin Proteins; D054808:Histatins; D054806:Magainins; D010455:Peptides; D012471:Salivary Proteins and Peptides; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus