|(übersetzt):||Antimicrobial Peptides (AMPs) are part of the immune system of vertebrates, they are promising candidates as lead structures for a new class of antibiotics. The first locus of interaction of AMPs with microorganisms is the cell membrane. In the case of Gram-negative bacteria this is the outer membrane, which is an asymmetric lipid bilayer, with a mixture of phospholipids on the inner and lipopolysaccharides (LPS) on the outer leaflet. The influence of the chemical structure of LPS on the barrier function of the outer membrane for the antimicrobial peptide LL32, a derivative of the human cathelicidin CAP18, is being investigated. Using Salmonella enterica serovar Minnesota rough mutants, which differ with respect to the length of the sugar moiety and the number of negative charges of their LPS, it was shown in biological killing assays that the rough mutants differed in their susceptibility towards LL32. Using different reconstitution systems (LPS-monolayers, LPS-aggregates, and in particular asymmetric planar lipid bilayers as a reconstitution system of the lipid matrix of the outer membrane), the interaction between LL32 and the isolated LPS of the respective mutants was charaterized. The biophysical data showed a clear dependence of the interaction between LL32 and LPS on LPS charge and the number of LPS core sugars. It could further be shown that LL32, added to the LPS side of asymmetric planar membranes, leads to the formation of lesions. This is in agreement with a self-promoted uptake of LL32 and accounts for the antibacterial action of LL32. There is a clear correlation between the biophysical and the biological data. The presented results show that LL32 interacts with the outer membrane of S. minnesota rough mutants and that the activity of LL32 depends on the LPS-structure.