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Evaluation of the antimicrobial activity in host-mimicking media and in vivo toxicity of antimicrobial polymers as functional mimics of AMPs

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Garcia Maset, Ramón, Hapeshi, Alexia, Hall, Stephen C. L., Dalgliesh, Robert M., Harrison, Freya and Perrier, Sébastien (2022) Evaluation of the antimicrobial activity in host-mimicking media and in vivo toxicity of antimicrobial polymers as functional mimics of AMPs. ACS Applied Materials & Interfaces, 14 (29). pp. 32855-32868. doi:10.1021/acsami.2c05979 ISSN 1944-8252.

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Official URL: https://doi.org/10.1021/acsami.2c05979

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Abstract

Activity tests for synthetic antimicrobial compounds are often limited to the minimal inhibitory concentration assay using standard media and bacterial strains. In this study, a family of acrylamide copolymers that act as synthetic mimics of antimicrobial peptides were synthesized and shown to have a disruptive effect on bacterial membranes and structural integrity through microscopy techniques and membrane polarization experiments. The polymers were tested for their antimicrobial properties using media that mimic clinically relevant conditions. Additionally, their activity was compared in two different strains of the Gram-positive bacterium Staphylococcus aureus and the Gram-negative bacterium Pseudomonas aeruginosa. We showed that the medium composition can have an important influence on the polymer activity as there was a considerable reduction in minimal inhibitory concentrations against S. aureus grown in synthetic wound fluid (SWF), and against P. aeruginosa grown in synthetic cystic fibrosis sputum media (SCFM), compared to the concentrations in standard testing media. In contrast, we observed a complete loss of activity against P. aeruginosa in the serum-containing SWF. Finally, we made use of an emerging invertebrate in vivo model, using Galleria mellonella larvae, to assess toxicity of the polymeric antimicrobials, showing a good correlation with cell line toxicity measurements and demonstrating its potential in the evaluation of novel antimicrobial materials.

Item Type: Journal Article
Divisions: Faculty of Science, Engineering and Medicine > Science > Chemistry
Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
SWORD Depositor: Library Publications Router
Journal or Publication Title: ACS Applied Materials & Interfaces
Publisher: American Chemical Society (ACS)
ISSN: 1944-8252
Official Date: 27 July 2022
Dates:
DateEvent
27 July 2022Published
12 July 2022Available
12 July 2022Accepted
Volume: 14
Number: 29
Page Range: pp. 32855-32868
DOI: 10.1021/acsami.2c05979
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Copyright Holders: Copyright © 2022 The Authors. Published by American Chemical Society
Date of first compliant deposit: 12 August 2022
Date of first compliant Open Access: 12 August 2022

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