Pathogen Membrane Interactions

Abstract

Unlike polyelectrolyte, amplipathic molecules interact with lipid membranes through electrostatic and hydrophobic interactions. Natural antimicrobial peptides and their synthetic derivatives are amphipathic molecules with broad-spectrum antimicrobial activity, but the underlying mechanism needs clarification. We systematically investigated interactions between model bacterial membranes and a prototypical family of phenylene ethynylene-based antimicrobial oligomers (AMO's) with controllable activity and selectivity. Homologues in this family can be inactive, specifically active against bacteria, or non-specifically active against bacteria and eukaryotic cells. Our results show that antibacterial activity correlates with ability to induce small unilamellar vesicles into an inverted hexagonal phase. Moreover, AMO's with different activity profiles require different minimum threshold concentration of PE lipids to reconstruct the membrane. To test the relevance of PE-requirement observed with model membranes to the activity of AMO, we carried out microbicidal assays in vitro against a PE knockout mutant bacteria strain and its wild-type parent strain. The results show that, although the PE deficient mutant is normally more susceptible than its wild-type parent strain, the mutant strain surprisingly out-survives its wild-type parental strain W3899 in the presence of our AMO, which is consistent with our results from model system.