The latest paper is now available on line via Biochemistry. Published by the American Chemical Society, we report a potentially novel bacterial resistance mechanism for the antimicrobial peptide Maximin H5 from Bombina maxima.
Host defense peptides show great potential for development as new antimicrobial agents however, a small number of resistance mechanisms are now being identified. In this case the peptide bound anionic and zwitterionic membranes with low affinity whilst showing a strong ability to lyse (>55%) and penetrate (π > 6.0 mN m–1) these membranes. However, the peptide bound Escherichia coli and 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) membranes with higher affinity and showed a very low ability for bilayer lysis (<8%) and partitioning (π > 1.0 mN m–1). Increasing levels of membrane DMPE correlated with enhanced binding by the peptide (R2 = 0.96) but inversely correlated with its lytic ability (R2 = 0.98). Taken with molecular dynamic simulations, these results suggest that maximin H5 forms multiple hydrogen bonds with phosphate and ammonium groups within PE head-groups, which in concert with charge–charge interactions anchor the peptide to the surface of E. coli membranes, inhibiting its membranolytic action.
Dennison et al http://pubs.acs.org/doi/abs/10.1021/bi400719j