Identification of the bactericidal domain of lactoferrin.
We report the existence of a previously unknown antimicrobial domain near the N-terminus of lactoferrin in a region distinct from its iron-binding sites. A single active peptide representing this domain was isolated following gastric pepsin cleavage of human lactoferrin, and bovine lactoferrin, and sequenced by automated Edman degradation. The antimicrobial sequence was found to consist mainly of a loop of 18 amino acid residues formed by a disulfide bond between cysteine residues 20 and 37 of human lactoferrin, or 19 and 36 of bovine lactoferrin. Synthetic analogs of this region similarly exhibited potent antibacterial properties. The active peptide of bovine lactoferrin was more potent than that of human lactoferrin having effectiveness against various Gram-negative and Gram-positive bacteria at concentrations between 0.3 microM and 3.0 microM, depending on the target strain. The effect of the isolated domain was lethal causing a rapid loss of colony-forming capability. Our studies suggest this domain is the structural region responsible for the bacterial properties of lactoferrin.
Bellamy
W
W
Nutritional Science Laboratory, Morinaga Milk Industry Company Limited, Zama City, Japan.
Takase
M
M
Yamauchi
K
K
Wakabayashi
H
H
Kawase
K
K
Tomita
M
M
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D004926:Escherichia coli / Q000187:drug effects*; D005260:Female; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects; D007781:Lactoferrin / Q000737:chemistry* / Q000494:pharmacology*; D008089:Listeria monocytogenes / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008892:Milk; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology; D011487:Protein Conformation; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012689:Sequence Homology, Nucleic Acid; D013211:Staphylococcus aureus / Q000187:drug effects
D010446:Peptide Fragments; D010455:Peptides; D007781:Lactoferrin