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Pseudotyping bacteriophage P2 tail fibers to extend the host range for biomedical applications
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Cunliffe, Tabitha G., Parker, Alan L. and Jaramillo, Alfonso (2022) Pseudotyping bacteriophage P2 tail fibers to extend the host range for biomedical applications. ACS Synthetic Biology, 11 (10). pp. 3207-3215. doi:10.1021/acssynbio.1c00629 ISSN 2161-5063.
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Official URL: https://doi.org/10.1021/acssynbio.1c00629
Abstract
Bacteriophages (phages) represent powerful potential treatments against antibiotic-resistant bacterial infections. Antibiotic-resistant bacteria represent a significant threat to global health, with an estimated 70% of infection-causing bacteria being resistant to one or more antibiotics. Developing novel antibiotics against the limited number of cellular targets is expensive and time-consuming, and bacteria can rapidly develop resistance. While bacterial resistance to phage can evolve, bacterial resistance to phage does not appear to spread through lateral gene transfer, and phage may similarly adapt through mutation to recover infectivity. Phages have been identified for all known bacteria, allowing the strain-selective killing of pathogenic bacteria. Here, we re-engineered the Escherichia coli phage P2 to alter its tropism toward pathogenic bacteria. Chimeric tail fibers formed between P2 and S16 genes were designed and generated through two approaches: homology- and literature-based. By presenting chimeric P2:S16 fibers on the P2 particle, our data suggests that the resultant phages were effectively detargeted from the native P2 cellular target, lipopolysaccharide, and were instead able to infect via the proteinaceous receptor, OmpC, the natural S16 receptor. Our work provides evidence that pseudotyping P2 is feasible and can be used to extend the host range of P2 to alternative receptors. Extension of this work could produce alternative chimeric tail fibers to target pathogenic bacterial threats. Our engineering of P2 allows adsorption through a heterologous outer-membrane protein without culturing in its native host, thus providing a potential means of engineering designer phages against pathogenic bacteria from knowledge of their surface proteome.
Item Type: | Journal Article | ||||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||
SWORD Depositor: | Library Publications Router | ||||||||
Journal or Publication Title: | ACS Synthetic Biology | ||||||||
Publisher: | American Chemical Society (ACS) | ||||||||
ISSN: | 2161-5063 | ||||||||
Official Date: | 21 October 2022 | ||||||||
Dates: |
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Volume: | 11 | ||||||||
Number: | 10 | ||||||||
Page Range: | pp. 3207-3215 | ||||||||
DOI: | 10.1021/acssynbio.1c00629 | ||||||||
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: | 24 October 2022 | ||||||||
Date of first compliant Open Access: | 24 October 2022 | ||||||||
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