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B5: The role of the glycostructure of amphiphilic membrane components for the interaction with antimicrobial peptides

Keywords: Gram-negative bacteria; lipopolysaccharide; antimicrobial peptid; cathelicidin; reconstituted membrane

The microbial membrane is the first target for antimicrobial peptides. The interaction of the peptides with the membrane can directly lead to its permeabilization or disintegration. Examples show that the lipid composition is crucial for the interaction. Thus, in many cases the sensitivity or resistance of microorganisms against a specific peptide is due to distinct differences in the chemical structure of the lipid matrices. Furthermore, differences in lipid membranes are also responsible for antimicrobial but not anti-host cell activities of drugs. The cell envelope of Gram-negative bacteria consists of the cytoplasmic membrane, the peptidoglycan layer, and an additional barrier, the outer membrane (OM) which is strictly asymmetric with respect to its lipid composition. Whereas the inner leaflet of this membrane contains only phospholipids, the outer leaflet is composed of lipopolysaccharides (LPS). This outer membrane is the primary target of many antibacterial peptides and in many cases it is also the locus of action. In other cases the drugs have to pass the OM to reach their final target.
In this project we investigate the influence of the composition and length of the sugar chain of the LPS on the fluidity and stability of the outer membrane and, moreover, its interaction with antimicrobial peptides. To probe membrane properties, we are establishing various biophysical techniques (e.g. fluorescence and atomic force microscopy). To determine the peptide induced membrane permeabilization, we use electrical measurements on planar membranes mimicking the asymmetric outer membrane of Gram-negative bacteria. We focus on alpha-helical polycationic peptides such as the human cathelicidins. For these peptides the structure parameters can be described more easily than for more complex molecules. The aim of this study is to establish structure-function relationships to optimize the activity of antimicrobial peptides against bacteria and to reduce the side effects against host cells.


Dr. Thomas Gutsmann / Prof. Dr. Ulrich Seydel

Forschungszentrum Borstel
Laborgruppe Biophysik
Parkallee 10
23845 Borstel

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