title: Mimicking and Understanding the Agglutination Effect of the Antimicrobial Peptide Thanatin Using Model Phospholipid Vesicles.
abstract: Thanatin is a cationic 21-residue antimicrobial and antifongical peptide found in the spined soldier bug Podisus maculiventris. It is believed that it does not permeabilize membranes but rather induces the agglutination of bacteria and inhibits cellular respiration. To clarify its mode of action, lipid vesicle organization and aggregation propensity as well as peptide secondary structure have been studied using different membrane models. Dynamic light scattering and turbidimetry results show that specific mixtures of negatively charged and zwitterionic phospholipid vesicles are able to mimic the agglutination effect of thanatin observed on Gram-negative and Gram-positive bacterial cells, while monoconstituent ("conventional") models cannot reproduce this phenomenon. The model of eukaryotic cell reveals no particular interaction with thanatin, which is consistent with the literature. Infrared spectroscopy shows that under the conditions under which vesicle agglutination occurs, thanatin exhibits a particular spectral pattern in the amide I' region and in the region associated with Arg side chains. The data suggest that thanatin mainly retains its hairpin structure, Arg residues being involved in strong interactions with anionic groups of phospholipids. In the absence of vesicle agglutination, the peptide conformation and Arg side-chain environment are similar to those observed in solution. The data show that a negatively charged membrane is required for thanatin to be active, but this condition is insufficient. The activity of thanatin seems to be modulated by the charge surface density of membranes and thanatin concentration.
authors.affiliation: Department of Chemistry, Regroupement québécois de recherche sur la fonction, la structure et l'ingénierie des protéines (PROTEO), Centre de recherche sur les matériaux avancés (CERMA), Centre québécois sur les matériaux fonctionnels (CQMF), Université Laval, Québec, QC, Canada G1V 0A6.
authors.forename: Émile
authors.initials: É
authors.lastname: Robert
authors.affiliation: Department of Chemistry, Regroupement québécois de recherche sur la fonction, la structure et l'ingénierie des protéines (PROTEO), Centre de recherche sur les matériaux avancés (CERMA), Centre québécois sur les matériaux fonctionnels (CQMF), Université Laval, Québec, QC, Canada G1V 0A6.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lefèvre
authors.affiliation: Department of Chemistry, Regroupement québécois de recherche sur la fonction, la structure et l'ingénierie des protéines (PROTEO), Centre de recherche sur les matériaux avancés (CERMA), Centre québécois sur les matériaux fonctionnels (CQMF), Université Laval, Québec, QC, Canada G1V 0A6.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Fillion
authors.affiliation: Department of Chemistry, Regroupement québécois de recherche sur la fonction, la structure et l'ingénierie des protéines (PROTEO), Centre de recherche sur les matériaux avancés (CERMA), Centre québécois sur les matériaux fonctionnels (CQMF), Université Laval, Québec, QC, Canada G1V 0A6.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Martial
authors.affiliation: Department of Chemistry, Regroupement québécois de recherche sur la fonction, la structure et l'ingénierie des protéines (PROTEO), Centre de recherche sur les matériaux avancés (CERMA), Centre québécois sur les matériaux fonctionnels (CQMF), Université Laval, Québec, QC, Canada G1V 0A6.
authors.forename: Justine
authors.initials: J
authors.lastname: Dionne
authors.affiliation: Department of Chemistry, Regroupement québécois de recherche sur la fonction, la structure et l'ingénierie des protéines (PROTEO), Centre de recherche sur les matériaux avancés (CERMA), Centre québécois sur les matériaux fonctionnels (CQMF), Université Laval, Québec, QC, Canada G1V 0A6.
authors.forename: Michèle
authors.initials: M
authors.lastname: Auger
mesh_terms: D000371:Agglutination; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology; D002462:Cell Membrane / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D010743:Phospholipids; C098076:thanatin