Antimicrobial peptides derived from heme-containing proteins: Hemocidins

Deprived of heme and partially unfolded hemoglobin, myoglobin and cytochrom e c display microbicidal activity against a broad spectrum of microorganism s with half maximal lethal dose estimated at micromolar concentrations. The intact proteins were ineffective. Antibacterial activity of these apohemop roteins 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) s howed 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 lipopolys accharide binding properties were observed. No hemolytic properties, even a t high peptide concentrations were found; however, a slight but dose-indepe ndent cytotoxic effect was observed on fibroblasts and hepatoma cells. The presented data suggest a 'carpet-like' mechanism of the membrane-directed a ctivity and may result from exceptional abilities of hemoprotein-derived pe ptides to form alpha-helical structures. We postulate that the antimicrobia l peptides obtained from the heme-containing proteins should be named hemoc idins, in contrast to, e.g., hemorphins displaying opioid-like activity.