Biophysical investigations into the interactions between antimicrobial peptides of the epithelial defense and microbial cell envelopes

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A prerequisite for antimicrobial peptides (AMPs) to kill bacteria is to destroy bacterial lipid membranes or to permeate them. We will investigate the interaction between AMPs of the epithelial defense system and natural or reconstituted lipid membranes. Recent results revealed different modes of action, which are highly peptide and lipid specific. We will concentrate on five topics within the context of peptide-lipid interactions: (1) Characterization of the molecular interaction mechanisms between certain natural AMPs and lipid membranes. (2) Synthesis of membrane-active peptides based on the natural AMPs. The goal is an increase of the antimicrobial activities, a reduction of cytotoxicity, and an increase of the neutralization of released bacterial virulence factors. (3) The possible induction of resistances of bacteria by the AMPs will be investigated in particular with respect to modifications of the lipid composition of the bacterial membranes. (4) In addition to the well established reconstitution models of the membranes of Gram-negative bacteria, respective reconstitution systems for the cell envelope of Gram-positive bacteria, archaea, and mycobacteria will be established. (5) Synergistic effects of membrane-active AMPs will be investigated in biological as well as in biophysical model systems.