This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Andrä, J.
Right arrow Articles by Brandenburg, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Andrä, J.
Right arrow Articles by Brandenburg, K.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, May 2004, p. 1593-1599, Vol. 48, No. 5
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.5.1593-1599.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Biophysical Characterization of Endotoxin Inactivation by NK-2, an Antimicrobial Peptide Derived from Mammalian NK-Lysin

Jörg Andrä,1* Michel H. J. Koch,2 Rainer Bartels,3 and Klaus Brandenburg1

Division of Biophysics,1 Division of Structural Biochemistry, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, D-23845 Borstel,3 European Molecular Biology Laboratory, Hamburg Outstation, EMBL c/o DESY, D-22603 Hamburg, Germany2

Received 30 September 2003/ Returned for modification 22 December 2003/ Accepted 29 January 2004

NK-2, a membrane-acting antimicrobial peptide, was derived from the cationic core region of porcine NK-lysin and consists of 27 amino acid residues. It adopts an amphipathic, {alpha}-helical secondary structure and has been shown to interact specifically with membranes of negatively charged lipids. We therefore investigated the interaction of NK-2 with lipopolysaccharide (LPS), the main, highly anionic component of the outer leaflet of the outer membrane of gram-negative bacteria, by means of biophysical and biological assays. As model organisms and a source of LPS, we used Salmonella enterica strains with various lengths of the LPS carbohydrate moiety, including smooth LPS, rough LPS, and deep rough LPS (LPS Re) mutant strains. NK-2 binds to LPS Re with a high affinity and induces a change in the endotoxin-lipid A aggregate structure from a cubic or unilamellar structure to a multilamellar one. This structural change, in concert with a significant overcompensation of the negative charges of LPS, is thought to result in the neutralization of the endotoxic LPS activity in a cell culture system. Neutralization of LPS activity by NK-2 as well as its antibacterial activity against the various Salmonella strains strongly depends on the length of the sugar chains of LPS, with LPS Re being the most sensitive. This suggests that a hydrophobic peptide-LPS interaction is necessary for efficient neutralization of the biological activity of LPS and that the long carbohydrate chains, besides their function as a barrier for hydrophobic drugs, also serve as a trap for polycationic substances.

* Corresponding author. Mailing address: Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Division of Biophysics, Parkallee 10, D-23845 Borstel, Germany. Phone: 49 (0) 4537-188 280. Fax: 49 (0) 4537-188 632. E-mail: jandrae{at}fz-borstel.de.

Antimicrobial Agents and Chemotherapy, May 2004, p. 1593-1599, Vol. 48, No. 5
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.5.1593-1599.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Andra, J., Monreal, D., de Tejada, G. M., Olak, C., Brezesinski, G., Gomez, S. S., Goldmann, T., Bartels, R., Brandenburg, K., Moriyon, I. (2007). Rationale for the Design of Shortened Derivatives of the NK-lysin-derived Antimicrobial Peptide NK-2 with Improved Activity against Gram-negative Pathogens. J. Biol. Chem. 282: 14719-14728 [Abstract] [Full Text]  
  • Andra, J., Gutsmann, T., Garidel, P., Brandenburg, K. (2006). Invited review: Mechanisms of endotoxin neutralization by synthetic cationic compounds. Innate Immunity 12: 261-277 [Abstract]  
  • Rosenfeld, Y., Papo, N., Shai, Y. (2006). Endotoxin (Lipopolysaccharide) Neutralization by Innate Immunity Host-Defense Peptides: PEPTIDE PROPERTIES AND PLAUSIBLE MODES OF ACTION. J. Biol. Chem. 281: 1636-1643 [Abstract] [Full Text]  
  • Bowdish, D. M.E., Hancock, R. E.W. (2005). Anti-endotoxin properties of cationic host defence peptides and proteins. Innate Immunity 11: 230-236 [Abstract]  
  • Papo, N., Shai, Y. (2005). A Molecular Mechanism for Lipopolysaccharide Protection of Gram-negative Bacteria from Antimicrobial Peptides. J. Biol. Chem. 280: 10378-10387 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»