Antibacterial activity of lactoferrin and a pepsin-derived lactoferrin peptide fragment

Abstract

Although the antimicrobial activity of lactoferrin has been well described, its mechanism of action has been poorly characterized. Recent work has indicated that in addition to binding iron, human lactoferrin damages the outer membrane of gram-negative bacteria. In this study, we determined whether bovine lactoferrin and a pepsin-derived bovine lactoferrin peptide (lactoferricin) fragment have similar activities. We found that both 20 ,uM bovine lactoferrin and 20 FM lactoferricin release intrinsicaly labeled [3HJlipopolysaccharide ([3H]LPS) from three bacterial strains, Escherichia coli CL9 1-2, SalnoneUa typhimurium SL696, and SalmonelUa montevideo SL5222. Under most conditions, more LPS is released by the peptide fragment than by whole bovine lactoferrin. In the presence of either lactoferrin or lactoferricin there is increased killing ofE. coli CL9 1-2 by lysozyme. Like human lactoferrin, bovine lactoferrin and lactoferricin have the ability to bind to free intrinsically labeled [3H]LPS molecules. In addition to these effects, whereas bovine lactoferrin was at most bacteriostatic, lactoferricin demonstrated consistent bactericidal activity against gram-negative bacteria. This bactericidal effect is modulated by the cations Ca2+, Mg2+, and Fe3+ but is independent of the osmolarity of the medium.

Lactoferrin a multiple bioactive protein: An overview

“…One of the first antimicrobial properties discovered for Lf was its role in sequestering iron from bacterial pathogens. This was believed to be the sole antimicrobial action of lactoferrin because apo-lactoferrin possessed antibacterial activity [31,32]. It was later demonstrated that lactoferrin can also kill microorganisms through an iron-independent mechanism [33] in which lactoferrin directly interacts with the bacterial cell surface [31,34,35].…”

Pathophysiology of Neonatal Sepsis

“…Lactoferrin is present in tears and saliva and has antimicrobial activity both via binding iron and by direct membrane disruption activity via a portion of its amino-terminal lactoferricin. 298 Lactoferrin is also an alarmin (e.g., HMGB-1 or IL-33), capable of activating leukocytes, binding endotoxin, and modifying the host response by acting as a transcription factor that regulates mRNA decay. 299,300 Bovine lactoferrin has been shown to reduce the incidence of bacterial and fungal sepsis 301,302 and NEC in preterm infants.…”

Influence of bovine lactoferrin and lactoferricin on cytokine expression in LPS‐treated cultivated bovine blood cells

“…Identical results were reported for bovine and human LFcin. 7,9 LPS, a bacterial endotoxin from the outer membrane of Gram-negative bacteria cell walls, has a high potency to stimulate inflammatory processes. 10,11 Mammals process a cluster of differentiation 14 (CD14) antigen-dependent pathways to detect LPS.…”