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Research Article Free access | 10.1172/JCI115407

Killing of gram-negative bacteria by lactoferrin and lysozyme.

R T Ellison 3rd and T J Giehl

Medical Service, Department of Veterans Affairs Medical Center, Denver, Colorado.

Find articles by Ellison, R. in: JCI | PubMed | Google Scholar

Medical Service, Department of Veterans Affairs Medical Center, Denver, Colorado.

Find articles by Giehl, T. in: JCI | PubMed | Google Scholar

Published October 1, 1991 - More info

Published in Volume 88, Issue 4 on October 1, 1991
J Clin Invest. 1991;88(4):1080–1091. https://doi.org/10.1172/JCI115407.
© 1991 The American Society for Clinical Investigation
Published October 1, 1991 - Version history
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Abstract

Although lactoferrin has antimicrobial activity, its mechanism of action is not full defined. Recently we have shown that the protein alters the Gram-negative outer membrane. As this membrane protects Gram-negative cells from lysozyme, we have studied whether lactoferrin's membrane effect could enhance the antibacterial activity of lysozyme. We have found that while each protein alone is bacteriostatic, together they can be bactericidal for strains of V. cholerae, S. typhimurium, and E. coli. The bactericidal effect is dose dependent, blocked by iron saturation of lactoferrin, and inhibited by high calcium levels, although lactoferrin does not chelate calcium. Using differing media, the effect of lactoferrin and lysozyme can be partially or completely inhibited; the degree of inhibition correlating with media osmolarity. Transmission electron microscopy shows that E. coli cells exposed to lactoferrin and lysozyme at 40 mOsm become enlarged and hypodense, suggesting killing through osmotic damage. Dialysis chamber studies indicate that bacterial killing requires direct contact with lactoferrin, and work with purified LPS suggests that this relates to direct LPS-binding by the protein. As lactoferrin and lysozyme are present together in high levels in mucosal secretions and neutrophil granules, it is probable that their interaction contributes to host defense.

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