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Quaternized polymer-based nanostructures confer antimicrobial efficacy against multidrug-resistant bacteria

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Abstract

The overuse of traditional antibiotics has resulted in a large number of bacteria that are resistant to antibiotics; therefore, the development of new antibacterial agents is urgently required to combat the drug-resistant bacteria. In this work, a series of cationic polyacrylate copolymers N1–N4 was synthesized by free-radical copolymerization. Amphiphilic N3 self-assembled into positively charged nanostructures (N3-NSs) with a diameter of 455.9 nm and a zeta potential of 33.4 mV in aqueous solution, which was confirmed by SEM and DLS. N3-NSs exhibited a broad-spectrum and high sterilization efficacy against both Gram-positive and Gram-negative bacteria, with a MIC value in the range of 2–8 μg mL−1 and a more than 94% sterilization rate against the drug-resistant E. coli, P. aeruginosa, E. faecalis, VRE, and B. subtilis tested. Most importantly, the nanostructures did not result in resistance of the VRE and P. aeruginosa even after their 16th passages. N3-NSs caused serious damage to E. coli and E. faecalis membranes, with significant loss of membrane potential from −43.9 ± 0.6 and −39.1 ± 1.4 to −6.3 ± 0.3 and −4.6 ± 0.2 mV, respectively. Fluorescence staining, SEM and membrane potential characterization reveal the action mechanism of the nanostructures, which is that N3-NSs initially bind to the surface of bacteria, then pierce into the bacterial membranes with their hydrophobic groups, and finally disrupt the membranes, therefore exhibiting broad-spectrum antibacterial efficacy. N3-NSs exhibit low toxicity on mouse fibroblasts (L929) at a dose of 40 μg mL−1. This work provides a promising way for the development of efficient antibacterial materials that do not cause drug-resistance.

Graphical abstract: Quaternized polymer-based nanostructures confer antimicrobial efficacy against multidrug-resistant bacteria

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Article information


Submitted
13 Dec 2019
Accepted
24 Jan 2020
First published
25 Jan 2020

New J. Chem., 2020, Advance Article
Article type
Paper

Quaternized polymer-based nanostructures confer antimicrobial efficacy against multidrug-resistant bacteria

M. Zhao, J. Zhen, K. Yang, Y. Liu, J. Li and S. Shi, New J. Chem., 2020, Advance Article , DOI: 10.1039/C9NJ06173H

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