Garcia Maset, R., Pasquina-Lemonche, L. orcid.org/0000-0002-8592-9542, Hapeshi, A. et al. (5 more authors) (2025) Assessing the mechanism of action of synthetic nanoengineered antimicrobial polymers against the bacterial membrane of Pseudomonas aeruginosa. Biomacromolecules. ISSN: 1525-7797
Abstract
The lack of appropriate antimicrobials to tackle multidrug-resistant Gram-negative bacteria poses an escalating threat to modern medicine. Addressing this urgent issue, we have recently developed synthetic nanoengineered antimicrobial polymers (SNAPs), inspired by the physicochemical properties of antimicrobial peptides. Our findings have demonstrated that SNAPs are potent antimicrobial agents characterized by low toxicity and cost-effective large-scale production. In this study, we elucidate the mechanism of action of two distinct SNAPs, which vary in length and charge distribution. Focusing on the Gram-negative pathogen Pseudomonas aeruginosa LESB58, a hypervirulent strain prevalent in cystic fibrosis patients, we employ advanced high-resolution imaging techniques and neutron reflectometry to uncover the precise interactions between SNAPs and the bacterial cell envelope. Our research identifies lipopolysaccharide as a critical target, detailing architecture-specific envelope disruptions, such as asymmetry loss, pore formation, and membrane dissolution. These insights into the structure-function relationships of SNAPs pave the way for the rational design of tailored antimicrobial polymers with specific targeted mechanisms of action.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025 The Authors. This publication is licensed under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/ |
Keywords: | Antimicrobial agents; Mechanisms of action; Membranes; Polymers; Vesicles |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) The University of Sheffield > Faculty of Science (Sheffield) > School of Mathematical and Physical Sciences |
Funding Information: | Funder Grant number WELLCOME TRUST (THE) 212197/Z/18/Z |
Date Deposited: | 08 Oct 2025 10:17 |
Last Modified: | 08 Oct 2025 10:17 |
Status: | Published online |
Publisher: | American Chemical Society (ACS) |
Refereed: | Yes |
Identification Number: | 10.1021/acs.biomac.5c01175 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:232665 |