The Clustering of Anionic Lipids by Highly Cationic Cell Penetrating Peptides, as with Antimicrobial Peptides, can Contribute to their Antimicrobial Activity

Abstract

It has been reported that there is some overlap of biological activities between cell penetrating peptides (CPPs) and antimicrobial peptides (AMPs). We have studied a group of 9 AMPs, a fusion peptide and 7 CPPs, with regard to their conformational state in the presence and absence of a lipid mixture mimicking the cytoplasmic composition of Gram negative bacteria, their ability to cluster anionic lipids and their bacteriostatic effect on several different species of bacteria. Generally those peptides with the highest number of charges per residue were more effective in clustering anionic lipids. Among the peptides studied, six AMPs and five CPPs were found to have anionic lipid clustering activity. Remarkably, these peptides also had bacteriostatic activity against several species of bacteria, particularly against E. coli, a Gram negative bacteria sensitive to lipid clustering agents. In contrast, those AMPs and CPPs that did not cluster anionic lipids were not toxic to E. coli. As shown for several types of AMPs previously, we suggest that anionic lipid clustering may contribute to the mechanism of antibacterial action of the more highly cationic CPPs as well. Furthermore, it is a mechanism that should be further considered to explain the entry of these agents into mammalian cells or their escape from intracellular endosomes.