Broad-spectrum antimicrobial activity of hemoglobin

While hemoglobin is one of the most well characterized proteins due tc, its function in oxygen transport, few additional properties of hemoglobin have been described. While screening serum samples for novel antimicrobial fact ors, it was found that intact hemoglobin tetramers, including that from hum an, exhibited considerable activity against gram-positive and gram-negative bacteria, and fungi. To further characterize this surprising activity, the antimicrobial potency of sections of human hemoglobin was tested against a panel of microorganisms. In all cases separate testing of the alpha and be ta subunits provided activity at least as potent as the intact tetramer. Th is activity is derived from the protein portion of hemoglobin since removal of the heme prosthetic group did not lead to decreases in potency. In addi tion, cyanogen bromide cleavage of both subunits provided fragments that st ill contained substantial antimicrobial activity. It has been possible to m ap specific regions of the human hemoglobin molecule that ore responsible f ur significant antimicrobial activity. The carboxyl terminal thirty amino a cids of the beta subunit, which form a cationic alpha -helix based on the c rystal structure of the intact tetramer, were active against Escherichia co li, Staphylococcus aureus and Candida albicans. In view of the fact that di fferent hemoglobin-derived peptide fragments exhibit diverse antibiotic act ivities, it is conceivable that, in addition to its role in oxygen transpor t, hemoglobin functions as an important multi-defense agent against a wide range of microorganisms. (C) 2001 Elsevier Science Ltd. All rights reserved .