Development of amyloid-cationic peptides with antimicrobial activities: Relation to their membranotropic activities.

Abstract

We describe here a new class of antimicrobial peptides (named Amy-Cat) comprised of a short amyloid domain and a cationic domain, as a primary amphipathic structure. The nona-arginine sequence was chosen as the cationic motif, while the sequence and size of the amyloid domain was modulated. The Amy-Cat peptides were found to be bactericidal against gram-negative and gram-positive standard bacterial strains with minimum inhibitory concentrations ranging from 3 to 24 μM, and being well-below their hemolytic concentrations. Their membranotropic activities were investigated as a function of the amyloid sequence and compared to those of the nona-arginine peptide. Calcein dye leakage on lipid mimic models for bacterial and eukaryotic membranes was carried out. In addition, the effect of the amyloid moiety on the membrane binding and on the conformational change were investigated at the buffer/supported lipid bilayer interface using ATR-FTIR spectroscopy. The overall findings suggest optimum routes to balancing the hydrophobicity of the amyloid sequence over the fixed cationic sequence allowing selective disruption of the bacterial membranes without eliciting hemolysis. Amy-Cat peptides appear to be very promising candidates for the development of new antimicrobial agents.