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Aryl-Alkyl-Lysines Interact with Anionic Lipid Components of Bacterial Cell Envelope Eliciting Anti-Inflammatory and Antibiofilm Properties.

ABSTRACT: The emergence of bacterial resistance and hesitance in approving new drugs has bolstered research on membrane-active agents such as antimicrobial peptides and their synthetic derivatives as therapeutic alternatives against bacterial infections. Herein, we document the action of aryl-alkyl-lysines on liposomes mimicking bacterial membranes using solid-state nuclear magnetic resonance spectroscopy. A significant perturbation of the lipid thickness and order parameter of the lipid membrane was observed upon treatment with this class of compounds. Encouraged by these results, the ability of the most active compound (NCK-10) to interact with aggregates of lipopolysaccharides (LPSs) was studied. In vitro experiments showed that NCK-10 was able to prevent the LPS-induced stimulation of proinflammatory cytokines such as tumor necrosis factor-? and interleukin-6. The compound could also disrupt the biofilms of Pseudomonas aeruginosa in vitro and bring down the bacterial burden by more than 99% in a mice model of burn infections caused by the biofilms of P. aeruginosa.

SUBMITTER: Ghosh C

PROVIDER: S-EPMC6645134 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Aryl-Alkyl-Lysines Interact with Anionic Lipid Components of Bacterial Cell Envelope Eliciting Anti-Inflammatory and Antibiofilm Properties.

Ghosh Chandradhish C Harmouche Nicole N Bechinger Burkhard B Haldar Jayanta J

ACS omega 20180815 8

The emergence of bacterial resistance and hesitance in approving new drugs has bolstered research on membrane-active agents such as antimicrobial peptides and their synthetic derivatives as therapeutic alternatives against bacterial infections. Herein, we document the action of aryl-alkyl-lysines on liposomes mimicking bacterial membranes using solid-state nuclear magnetic resonance spectroscopy. A significant perturbation of the lipid thickness and order parameter of the lipid membrane was obse ...[more]

PMID: 31459052

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Project description:Natural or synthetic polycations are used as biocides or as drug/gene carriers. Understanding the interactions between these macromolecules and cell membranes at the molecular level is therefore of great importance for the design of effective polymer biocides or biocompatible polycation-based delivery systems. Until now, details of the processes at the interface between polycations and biological systems have not been fully recognized. In this study, we consider the effect of strong polycations with quaternary ammonium groups on the properties of anionic lipid membranes that we use as a model system for protein-free cell membranes. For this purpose, we employed experimental measurements and atomic-scale molecular dynamics (MD) simulations. MD simulations reveal that the polycations are strongly hydrated in the aqueous phase and do not lose the water shell after adsorption at the bilayer surface. As a result of strong hydration, the polymer chains reside at the phospholipid headgroup and do not penetrate to the acyl chain region. The polycation adsorption involves the formation of anionic lipid-rich domains, and the density of anionic lipids in these domains depends on the length of the polycation chain. We observed the accumulation of anionic lipids only in the leaflet interacting with the polymer, which leads to the formation of compositionally asymmetric domains. Asymmetric adsorption of the polycation on only one leaflet of the anionic membrane strongly affects the membrane properties in the polycation-membrane contact areas: (i) anionic lipid accumulates in the region near the adsorbed polymer, (ii) acyl chain ordering and lipid packing are reduced, which results in a decrease in the thickness of the bilayer, and (iii) polycation-anionic membrane interactions are strongly influenced by the presence and concentration of salt. Our results provide an atomic-scale description of the interactions of polycations with anionic lipid bilayers and are fully supported by the experimental data. The outcomes are important for understanding the correlation of the structure of polycations with their activity on biomembranes.

Dataset Information

Aryl-Alkyl-Lysines Interact with Anionic Lipid Components of Bacterial Cell Envelope Eliciting Anti-Inflammatory and Antibiofilm Properties.

Publications

Aryl-Alkyl-Lysines Interact with Anionic Lipid Components of Bacterial Cell Envelope Eliciting Anti-Inflammatory and Antibiofilm Properties.

Similar Datasets

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