title: Peptoids successfully inhibit the growth of gram negative E. coli causing substantial membrane damage.
abstract: Peptoids are an alternative approach to antimicrobial peptides that offer higher stability towards enzymatic degradation. It is essential when developing new types of peptoids, that mimic the function of antimicrobial peptides, to understand their mechanism of action. Few studies on the specific mechanism of action of antimicrobial peptoids have been described in the literature, despite the plethora of studies on the mode of action of antimicrobial peptides. Here, we investigate the mechanism of action of two short cationic peptoids, rich in lysine and tryptophan side chain functionalities. We demonstrate that both peptoids are able to cause loss of viability in E. coli susceptible cells at their MIC (16-32 μg/ml) concentrations. Dye leakage assays demonstrate slow and low membrane permeabilization for peptoid 1, that is still higher for lipid compositions mimicking bacterial membranes than lipid compositions containing Cholesterol. At concentrations of 4 × MIC (64-128 μg/ml), pore formation, leakage of cytoplasmic content and filamentation were the most commonly observed morphological changes seen by SEM in E. coli treated with both peptoids. Flow cytometry data supports the increase of cell size as observed in the quantification analysis from the SEM images and suggests overall decrease of DNA per cell mass over time.
authors.affiliation: Department of Science and Environment, Roskilde University, Universitetsvej 1, Postboks 260,4000 Roskilde, Denmark.
authors.forename: Biljana
authors.initials: B
authors.lastname: Mojsoska
authors.affiliation: Department of Science and Environment, Roskilde University, Universitetsvej 1, Postboks 260,4000 Roskilde, Denmark.|Department of Biochemistry, Institute of Chemistry. University of São Paulo, São Paulo, Brazil.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Carretero
authors.affiliation: Department of Science and Environment, Roskilde University, Universitetsvej 1, Postboks 260,4000 Roskilde, Denmark.|Department of Clinical Immunology, Naestved Hospital, Naestved, Denmark.
authors.forename: Sylvester
authors.initials: S
authors.lastname: Larsen
authors.affiliation: DTU CEN, Center for Electron Nanoscopy, Technical University of Denmark, Kgs Lyngby, Denmark.
authors.forename: Ramona Valentina
authors.initials: RV
authors.lastname: Mateiu
authors.affiliation: Department of Science and Environment, Roskilde University, Universitetsvej 1, Postboks 260,4000 Roskilde, Denmark.
authors.forename: Håvard
authors.initials: H
authors.lastname: Jenssen
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004269:DNA, Bacterial / Q000378:metabolism; D004926:Escherichia coli / Q000166:cytology / Q000187:drug effects / Q000254:growth & development* / Q000648:ultrastructure; D005452:Fluoresceins / Q000737:chemistry / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry; D007700:Kinetics; D008081:Liposomes / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D034444:Peptoids / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008081:Liposomes; D034444:Peptoids; C024098:6-carboxyfluorescein; C007740:fluorexon