Journal of Endotoxin Research

 

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Journal of Endotoxin Research, Vol. 9, No. 2, 67-84 (2003)
DOI: 10.1177/09680519030090020101


Reviews

Review: Towards antibacterial strategies: studies on the mechanisms of interaction between antibacterial peptides and model membranes

Andre Wiese

Division of Biophysics, Research Center Borstel, Borstel, Germany

Thomas Gutsmann

Division of Biophysics, Research Center Borstel, Borstel, Germany

Ulrich Seydel

Division of Biophysics, Research Center Borstel, Borstel, Germany, useydel{at}fz-borstel.de

Lipopolysaccharides (LPSs) play a dual role as inflammation-inducing and as membrane-forming molecules. The former role attracts significantly more attention from scientists, possibly because it is more closely related to sepsis and septic shock. This review aims to focus the reader's attention to the other role, the function of LPS as the major constituent of the outer layer of the outer membrane of Gram-negative bacteria, in particular those of enterobacterial strains. In this function, LPS is a necessary component of the cell envelope and guarantees survival of the bacterial organism. At the same time, it represents the first target for attacking molecules which may either be synthesized by the host's innate or adaptive immune system or administered to the human body. The interaction of these molecules with the outer membrane may not only directly cause the death of the bacterial organism, but may also lead to the release of LPS into the circulation. Here, we review membrane model systems and their application for the study of molecular mechanisms of interaction of peptides such as those of the human complement system, the bactericidal/permeability-increasing protein (BPI), cationic antibacterial peptide 18 kDa (CAP18) as an example of cathelicidins, defensins, and polymyxin B (PMB). Emphasis is on electrical measurements with a reconstitution system of the lipid matrix of the outer membrane which was established in the authors' laboratory as a planar asymmetric bilayer with one leaflet being composed solely of LPS and the other of the natural phospholipid mixture. The main conclusion, which can be drawn from these investigations, is that LPS and in general its negative charges are the dominant determinants for specific peptide—membrane interactions. However, the detailed mechanisms of interaction, which finally lead to bacterial killing, may involve further steps and differ for different antibacterial peptides.


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