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.

Antibacterial mechanisms of GN‐2 derived peptides and peptoids against Escherichia coli

“…Preliminary studies had demonstrated that the peptoids GN‐2, GN‐2‐ N lys 1‐4 N trp 5‐8 and GN‐2‐ N pm 9 were valid antimicrobials (Table and Figure ), as they successfully inhibited the growth of E. coli by causing substantial membrane damage . However, as stated before, the peptide GN‐2 and the peptoid GN‐2 are not exactly analogues .…”

“…This study investigated the E. coli antibiofilm properties of peptide and peptoid variants modeled upon the synthetic peptide GN‐2, previously reported as a successful antimicrobial agent within a cohort of peptides generated through a QSAR‐based in silico approach . Preliminary studies reported the ability of peptoids GN‐2‐ N lys 1‐4 N trp 5‐8 and GN‐2‐ N pm 9 (Figure ) to inhibit the growth of E. coli , by disrupting its membrane integrity; however, their activity against E. coli biofilms was not investigated. In addition, a new set of peptide variants of these successful peptoids was synthetized to assess whether the antimicrobial potential was maintained in the transition from peptoid to peptide and to further clarify the antibacterial effects of lysine to arginine and phenylalanine to isoleucine substitutions in the sequence.…”

Solar light induced antibacterial performance of TiO2 crystallized glass ceramics

“…The TiO 2 crystallized glass generates surface electron (e − ) and hole (h + ) which results in the peroxidation of cell wall membranes . Degradation of the cell wall alters the selective permeability of cell membrane and increases the pressure inside the cell which leads to cytolysis . ROS produced due to microelectrolysis of water molecules in the system enters into cells and increases the oxidative stress inside the cells.…”

Peptoid drug discovery and optimization via surface X‐ray scattering

“…There are several mechanisms of membrane disruption in bacteria described for AMPs including barrel‐stave, carpet‐like, and formation of toroidal pores, yet none of them have been confirmed for peptoid substituents. Membrane damaging effect is suggested to be the primary mode of action by peptoids, while the potential intracellular targeting of ATP efflux, ribosome aggregation, enzymatic and mitochondrial activity, as well as nucleic acid synthesis, might be also involved. Peptoid amphipathic topology allows for electrostatic binding toward the lipid phosphate groups, implicated in membrane depolarization .…”