Biophysical Characterization And Membrane Interactions Of Peptides With Antimicrobial Potential

Abstract

It has been estimated that multiresistant bacteria present in hospitals are responsible for 2.5 millions of infections and of several thousands deaths each year in North America. The development of new classes of antibiotics is thus very important to fight against these bacteria. Amphipathic peptides with cationic charges represent one of these new classes. These peptides act by disrupting negatively charged bacterial membranes and have less effect on neutral eukaryotic plasma membrane.We have previously shown that a non-natural peptide composed of 14 non charged residues (10 leucines and 4 phenylalanines modified with a crown ether) is able to disrupt bilayers but without selectivity (1, 2).To gain specificity against negatively charged membranes, several leucines of this 14-mer have been substituted by positively charged residues (lysine, arginine, histidine). Biological tests indicate that some peptides are active against E. coli but ineffective against human red cells. These compounds have thus interesting properties to be use as antibiotics in the future.In our group, we study these peptides by biophysical methods in order to better understand their mode of action on membranes. Fluorescence and Fourier transform infrared spectroscopies studies indicate that selective peptides disrupt negatively charged membranes but have no effect on neutral membranes. These methods, as well as dynamic light scattering and solid-state NMR also suggest that the peptides induce pore formation in the target membranes. This ability is related to the ability of peptides to be mainly in alpha-helix structure.References :1) Y.R. Vandenburg, B.D. Smith, E. Biron, N. Voyer (2002) Chem Commun (Camb). 21:1694-1695.2) M. Ouellet, F. Otis, N. Voyer, M. Auger (2006) Biochim Biophys Acta. 1758:1235-1244.