Peptoids successfully inhibit the growth of gram negative E. coli causing substantial membrane damage

Mojsoska, Biljana; Carretero, Gustavo; Larsen, Sylvester; Mateiu, Ramona Valentina; Jenssen, Håvard

doi:10.1038/srep42332

Title: Peptoids successfully inhibit the growth of gram negative E. coli causing substantial membrane damage

Journal Article · Tue Feb 14 00:00:00 EST 2017 · Scientific Reports

DOI:https://doi.org/10.1038/srep42332· OSTI ID:1624888

Mojsoska, Biljana ^[1]; Carretero, Gustavo ^[1]; Larsen, Sylvester ^[2]; Mateiu, Ramona Valentina ^[3]; Jenssen, Håvard ^[1]

Roskilde University, Roskilde (Denmark), Dept. of Science and Environment
Roskilde University, Roskilde (Denmark), Dept. of Science and Environment; Naestved Hospital, Naestved (Denmark). Department of Clinical Immunology
University of São Paulo, São Paulo (Brazil). Department of Biochemistry, Institute of Chemistry; Technical University of Denmark, Kgs Lyngby (Denmark). DTU CEN, Center for Electron Nanoscopy

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.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1624888

Journal Information:: Scientific Reports, Vol. 7, Issue 1; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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