Dennison, Sarah Rachel, Harris, Frederick, Mura, Manuela, Morton, Leslie H. G., Zvelindovsky, Andrei and Phoenix, David Andrew (2013) A novel form of bacterial resistance to the action of eukaryotic host defense peptides, the use of a lipid receptor. Biochemistry, 52 (35). pp. 6021-6029. ISSN 0006-2960
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Official URL: http://dx.doi.org/10.1021/bi400719j
Host defense peptides show great potential for development as new antimicrobial agents with novel mechanisms of action. However, a small number of resistance mechanisms to their action are known, and here, we report a novel bacterial resistance mechanism mediated by a lipid receptor. Maximin H5 from Bombina maxima bound anionic and zwitterionic membranes with low affinity (Kd > 225 μM) while 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 (Kd < 65 μM) 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 possesses membranolytic activity, primarily involving bilayer insertion of its strongly hydrophobic N-terminal region. However, this region was predicted to form 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.
|Schools:||Faculty of Clinical & Biomedical Sciences > School of Pharmacy and Biomedical Sciences|
|Deposited By:||Simone Finley|
|Deposited On:||22 Oct 2013 09:14|
|Last Modified:||15 Mar 2017 10:44|
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