Antimicrobial peptides derived from heme-containing proteins: hemocidins.
Deprived of heme and partially unfolded hemoglobin, myoglobin and cytochrome c display microbicidal activity against a broad spectrum of microorganisms with half maximal lethal dose estimated at micromolar concentrations. The intact proteins were ineffective. Antibacterial activity of these apohemoproteins was also sustained after digestion to approximately 50 amino acids long peptides but further fragmentation abolished microbicidal properties. The most active fragment of apomyoglobin (corresponding to 56-131 region) showed a pronounced effect on the E. coli membrane permeabilization and its action was sensitive to salt as well as to divalent cations concentrations. The membrane-directed effect was specific toward bacteria but no lipopolysaccharide binding properties were observed. No hemolytic properties, even at high peptide concentrations were found; however, a slight but dose-independent cytotoxic effect was observed on fibroblasts and hepatoma cells. The presented data suggest a 'carpet-like' mechanism of the membrane-directed activity and may result from exceptional abilities of hemoprotein-derived peptides to form alpha-helical structures. We postulate that the antimicrobial peptides obtained from the heme-containing proteins should be named hemocidins, in contrast to, e.g., hemorphins displaying opioid-like activity.
Mak
P
P
Institute of Molecular Biology, Jagiellonian University, Mickiewicza 3, 31-120 Kraków, Poland.
Wójcik
K
K
Silberring
J
J
Dubin
A
A
D000890:Anti-Infective Agents / Q000737:chemistry* / Q000302:isolation & purification* / Q000633:toxicity; D001419:Bacteria / Q000187:drug effects*; D002175:Candida / Q000187:drug effects*; D002413:Cations, Divalent / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D045304:Cytochromes c / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D005347:Fibroblasts / Q000187:drug effects; D006454:Hemoglobins / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D006461:Hemolysis; D022781:Hepatocytes / Q000187:drug effects; D008070:Lipopolysaccharides / Q000378:metabolism; D009211:Myoglobin / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D010455:Peptides / Q000494:pharmacology* / Q000633:toxicity; D010539:Permeability / Q000187:drug effects; D011485:Protein Binding; D012965:Sodium Chloride / Q000378:metabolism
D000890:Anti-Infective Agents; D002413:Cations, Divalent; D006454:Hemoglobins; D008070:Lipopolysaccharides; D009211:Myoglobin; D010455:Peptides; D012965:Sodium Chloride; D045304:Cytochromes c