Membrane Interactions with ATRA Peptides

Abstract

The “catastrophic threat” of antibiotic resistance has prompted research into biological methods of combating bacterial infection. One such pervasive strategy employs cationic antimicrobial peptides, CAMPs. These peptides use their structure to target and disrupt bacterial membranes. The cationic peptides are specifically attracted to bacteria because of the high anionic lipid content in the outer leaflet of bacterial membranes. Most have already been shown to have broad spectrum activity, adequate potency, and minimal resistance. Considering these peptides have been active against pathogens for millions of years and have not developed any broad resistance, they are of particular interest to study. One class of CAMPs, AHCAPs, forms amphipathic α-helices when in the presence of anionic membranes. The peptide NA-CATH, from the Naja atra snake, and its analog, ATRA-1A, show promising activity. We are currently examining the effect of lipid composition and peptide chirality (L and D isomers) on peptide activity and membrane interactions. Kinetic assays show increased activity with increasing peptide concentration and match the EC50 (50% of maximal dose) trends for zwitterionic/anionic lipid composition.