Targeting intracellular, multi-drug resistant Staphylococcus aureus with guanidinium polymers by elucidating the structure-activity relationship
- Intracellular persistence of bacteria represents a clinical challenge as bacteria can thrive in an environment protected from antibiotics and immune responses. Novel targeting strategies are critical in tackling antibiotic resistant infections. Synthetic antimicrobial peptides (SAMPs) are interesting candidates as they exhibit a very high antimicrobial activity. We first compared the activity of a library of ammonium and guanidinium polymers with different sequences (statistical, tetrablock and diblock) synthesized by RAFT polymerization against methicillin-resistant S. aureus (MRSA) and methicillin-sensitive strains (MSSA). As the guanidinium SAMPs were the most potent, they were used to treat intracellular S. aureus in keratinocytes. The diblock structure was the most active, reducing the amount of intracellular MSSA and MRSA by two-fold. We present here a potential treatment for intracellular, multi-drug resistant bacteria, using a simple and scalable strategy.
Author details: | Agnes KurokiORCiD, Arnaud Kengmo TchoupaORCiD, Matthias HartliebORCiDGND, Raoul PeltierORCiD, Katherine E. S. LocockORCiD, Meera UnnikrishnanORCiD, Sebastien PerrierORCiD |
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DOI: | https://doi.org/10.1016/j.biomaterials.2019.119249 |
ISSN: | 0142-9612 |
ISSN: | 1878-5905 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/31279102 |
Title of parent work (English): | Biomaterials : biomaterials reviews online |
Publisher: | Elsevier |
Place of publishing: | Oxford |
Publication type: | Article |
Language: | English |
Year of first publication: | 2019 |
Publication year: | 2019 |
Release date: | 2020/11/04 |
Tag: | Antimicrobial; Block copolymers; Intracellular bacteria; RAFT polymerization |
Volume: | 217 |
Number of pages: | 13 |
Funding institution: | CSIRO PhD scholarship scheme; CSIRO Julius Career Award; German Research Foundation (DFG)German Research Foundation (DFG) [GZ: HA 7725/1-1]; Royal Society Wolfson Merit AwardRoyal Society of London [WM130055]; Monash-Warwick Alliance |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Chemie |
DDC classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
Peer review: | Referiert |