Broad-spectrum antimicrobial activity of hemoglobin.
While hemoglobin is one of the most well characterized proteins due to its function in oxygen transport, few additional properties of hemoglobin have been described. While screening serum samples for novel antimicrobial factors, it was found that intact hemoglobin tetramers, including that from human, 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 beta subunits provided activity at least as potent as the intact tetramer. This activity is derived from the protein portion of hemoglobin since removal of the heme prosthetic group did not lead to decreases in potency. In addition, cyanogen bromide cleavage of both subunits provided fragments that still contained substantial antimicrobial activity. It has been possible to map specific regions of the human hemoglobin molecule that are responsible for significant antimicrobial activity. The carboxyl terminal thirty amino acids of the beta subunit, which form a cationic alpha-helix based on the crystal structure of the intact tetramer, were active against Escherichia coli, Staphylococcus aureus and Candida albicans. In view of the fact that different hemoglobin-derived peptide fragments exhibit diverse antibiotic activities, it is conceivable that, in addition to its role in oxygen transport. hemoglobin functions as an important multi-defense agent against a wide range of microorganisms.
Department of Chemistry, Columbia University, New York, NY 10027, USA.
C A
CA
Parish
H
H
Jiang
Y
Y
Tokiwa
N
N
Berova
K
K
Nakanishi
D
D
McCabe
W
W
Zuckerman
M M
MM
Xia
J E
JE
Gabay
D000818:Animals; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D003488:Cyanogen Bromide / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D010446:Peptide Fragments / Q000302:isolation & purification / Q000494:pharmacology; D017433:Protein Structure, Secondary; D021122:Protein Subunits; D011524:Protoporphyrins / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D006454:Hemoglobins; D010446:Peptide Fragments; D021122:Protein Subunits; D011524:Protoporphyrins; D003488:Cyanogen Bromide