Elastic behavior of model membranes with antimicrobial peptides depends on lipid specificity and d -enantiomers

DUPUY, FERNANDO G.; MOODY, DIAMOND; MONTELARO, RONALD C.; ARSOV, ZORAN; ERNST, ROBERT K.; PETER DI, Y.; KUMAGAI, AKARI; ELHADY, YASMENE; DESLOUCHES, BERTHONY; TRISTRAM-NAGLE, STEPHANIE

SOFT MATTER

ROYAL SOC CHEMISTRY

Lugar: CAMBRIDGE; Año: 2019 vol. 15 p. 1860 - 1868

1744-683X

In an effort to provide new treatments for the global crisis of bacterial resistance to current antibiotics, we have used a rational approach to design several new antimicrobial peptides (AMPs). The present study focuses on 24-mer WLBU2 and its derivative, D8, with the amino acid sequence, RRWVRRVRRWVRRVVRVVRRWVRR. In D8, all of the valines are the D-enantiomer. We use X-ray low- and wide-angle diffuse scattering data to measure elasticity and lipid chain order. We show a good correlation between in vitro bacterial killing efficiency and both bending and chain order behavior in bacterial lipid membrane mimics; our results suggest that AMP-triggered domain formation could be the mechanism of bacterial killing in both Gram-positive and Gram-negative bacteria. In red blood cell lipid mimics, D8 stiffens and orders the membrane, while WLBU2 softens and disorders it, which correlate with D8´s harmless vs. WLBU2´s toxic behavior in hemolysis tests. These results suggest that elasticity and chain order behavior can be used to predict mechanisms of bactericidal action and toxicity of new AMPs.