9. Membrane Interactions of Proline-Rich Antimicrobial Peptide, Chex1-Arg20, Multimers
Abstract:
The increasing prevalence of antibiotic-resistant pathogens requires the development of new antibiotics. Proline-rich antimicrobial peptides (PrAMPs), including native apidaecins, Bac7, and oncocins or designed A3APO, show multi-modal actions against pathogens together with immunostimulatory activities. The interactions of the designed PrAMP, Chex1-Arg20, and its dimeric and tetrameric oligomers with different model membranes were investigated by circular dichroism spectroscopy, dynamic light scattering, zeta potential, differential scanning calorimetry, and dye leakage. Chex1-Arg20 oligomers showed stronger affinity and preferential binding to negatively charged phospholipid bilayers and led to lipid aggregation and neutralization. Fluorescence microscopy of negatively charged giant unilamellar vesicles with AlexFluor-647-labeled Chex1-Arg20 dimers and tetramers displayed aggregation at a peptide/lipid low ratio of 1:200 and at higher peptide concentrations (1:100/1:50) for Chex1-Arg20 monomer. Such interactions, aggregation, and neutralization of PrAMP oligomers additionally showed the importance of interactions of PrAMPs with negatively charged membranes.
Li, W.; Sani, M-A.; Jamasbi, E; Otvos, L.; Hossain, M. A.; Wade, J. D.; Separovic, F.* (2016): Membrane interactions of proline-rich antimicrobial peptide, Chex1-Arg20, multimers. Biochim. Biophys. Acta, 1858, 1236-1243, DOI: 10.1016/j.bbamem.2016.02.035.
