title: Hydramacin-1 in action: scrutinizing the barnacle model.
abstract: Hydramacin-1 (HM1) from the metazoan Hydra exerts antimicrobial activity against a wide range of bacterial strains. Notably, HM1 induces the aggregation of bacterial cells, accompanied by precipitation. To date, the proposed mechanism of peptide-lipid interaction, termed the barnacle model, has not been described on the molecular level. Here, we show by biochemical and biophysical techniques that the lipid-peptide interactions of HM1 are initiated by electrostatic and hydrophobic effects, in particular, by tryptophan and neighboring polar amino acid residues that cause an interfacial localization of the peptide between two self-contained lipid bilayers. The high binding constants of HM1 upon lipid interaction are in the range of other potent antimicrobial peptides, e.g., magainin, and can be reasonably explained by two distinct epitopes on the surface of the peptide's global structure, which both contain SWT(K/R) motifs. The residues of this motif favor localization of the peptide in the head group region of phospholipid bilayers up to a penetration depth of 4 Å and a minor participation of the lipids' hydrocarbon regions. Our results expand the knowledge about the molecular modes of action antimicrobial peptides use to tackle their target cells. Furthermore, the aggregation of living bacteria by HM1 was observed for a broad range of Gram-positive and Gram-negative bacteria. Therefore, the detailed view of peptide-lipid interactions described by the barnacle model consolidates it among the established models.
authors.affiliation: Université de Strasbourg/CNRS, UMR7177, Institut de Chimie, Strasbourg, France.
authors.forename: Matthias
authors.initials: M
authors.lastname: Michalek
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincent
authors.forename: Rainer
authors.initials: R
authors.lastname: Podschun
authors.forename: Joachim
authors.initials: J
authors.lastname: Grötzinger
authors.forename: Burkhard
authors.initials: B
authors.lastname: Bechinger
authors.forename: Sascha
authors.initials: S
authors.lastname: Jung
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000378:metabolism; D016956:Burkholderia cepacia / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008055:Lipids; D011485:Protein Binding; D011513:Proteus mirabilis / Q000187:drug effects / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism; D041162:Staphylococcus haemolyticus / Q000187:drug effects / Q000378:metabolism; D041181:Staphylococcus hominis / Q000187:drug effects / Q000378:metabolism; D055672:Static Electricity; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D008055:Lipids; C539006:hydramacin-1, Hydra magnipapillata