Margitta Dathe
Leibniz Institute of Molecular Pharmacology, Germany
Title: The secrets and potential of a novel cyclic antimicrobial and cell penetrating peptide
Biography
Biography: Margitta Dathe
Abstract
The synthetic cyclic hexapeptide cWFW (cyclo(RRRWFW)) is very stable towards proteolytic degradation, low pH and has a high activity against different Gram positive and Gram negative laboratory strains and clinical pathogens, including S. aureus and L. monocytogenes. With its amphipathic structure and high content of arginine residues, the peptide combines the prerequisites for membrane permeabilisation and membrane translocation as modes of action [1-3]. Using a number of techniques to study peptide interaction with bacterial and eukaryotic model membranes as well as with bacterial and eukaryotic cells, we could show that the activity of cWFW is based on a novel antimicrobial mechanism. Strong interactions with the bacterial membrane lead to reduction in membrane fluidity and disturbance of the native lipid matrix. The formation of distinct lipid domains is related to a severe disturbance in the positioning of functional proteins which finally leads to cell death. While the peptide does not enter the cytoplasm of bacteria, cWFW is rapidly internalized into human cells without decreasing cell viability. The combination of cell penetrating properties with high antimicrobial activity and the novel mechanism of action renders the cyclic hexapeptide an eligible compound with regard to the treatment of intracellular bacterial infections, as e.g. in the case of tuberculosis and pneumonia