Concilio, Matilde, Garcia Maset, Ramón, Lemonche, Laia Pasquina, Kontrimas, Vito, Song, Ji‐Inn, Rajendrakumar, Santhosh Kalash, Harrison, Freya, Becer, C. Remzi and Perrier, Sébastien (2023) Mechanism of action of oxazoline‐based antimicrobial polymers against staphylococcus aureus : in vivo antimicrobial activity evaluation. Advanced Healthcare Materials . 2301961. doi:10.1002/adhm.202301961 ISSN 2192-2659.
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Abstract
Antimicrobial‐resistant pathogens have reached alarming levels, becoming one of the most pressing global health issues. Hence, new treatments are necessary for the fight against antimicrobial resistance. Synthetic nanoengineered antimicrobial polymers (SNAPs) have emerged as a promising alternative to antimicrobial peptides, overcoming some of their limitations while keeping their key features. Herein, a library of amphiphilic oxazoline‐based SNAPs using cationic ring‐opening polymerization (CROP) is designed. Amphipathic compounds with 70% cationic content exhibit the highest activity against clinically relevant Staphylococcus aureus isolates, maintaining good biocompatibility in vitro and in vivo. The mechanism of action of the lead compounds against S. aureus is assessed using various microscopy techniques, indicating cell membrane disruption, while the cell wall remains unaffected. Furthermore, a potential interaction of the compounds with bacterial DNA is shown, with possible implications on bacterial division. Finally, one of the compounds exhibits high efficacy in vivo in an insect infection model.
| Item Type: | Journal Article |
|---|---|
| Subjects: | Q Science > QR Microbiology R Medicine > RM Therapeutics. Pharmacology |
| 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 |
| Library of Congress Subject Headings (LCSH): | Antibiotics, Drug resistance in microorganisms, Staphylococcus aureus, Antibacterial agents, Polymers in medicine |
| Journal or Publication Title: | Advanced Healthcare Materials |
| Publisher: | Wiley |
| ISSN: | 2192-2659 |
| Official Date: | 6 September 2023 |
| Dates: | Date Event 6 September 2023 Published 31 July 2023 Available 1 July 2023 Accepted |
| Article Number: | 2301961 |
| DOI: | 10.1002/adhm.202301961 |
| Status: | Peer Reviewed |
| Publication Status: | Published |
| Access rights to Published version: | Open Access (Creative Commons open licence) |
| Date of first compliant deposit: | 19 September 2023 |
| Date of first compliant Open Access: | 19 September 2023 |
| RIOXX Funder/Project Grant: | Project/Grant ID RIOXX Funder Name Funder ID |
| Related URLs: | |
| URI: | https://wrap.warwick.ac.uk/179066/ |
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