Designing P. aeruginosa synthetic phages with reduced genomes
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s41598-021-81580-2.pdf
Description
Published version
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2.05 MB
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Checksum (MD5)
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Author(s)
Pires, Diana P
Monteiro, Rodrigo
Mil-Homens, Dalila
Fialho, Arsénio
Lu, Timothy K
Azeredo, Joana
Date Issued
2021
Journal
Scientific Reports
Publisher
Springer Science and Business Media LLC
Citation
Pires, Diana P, Monteiro, Rodrigo, Mil-Homens, Dalila, Fialho, Arsénio, Lu, Timothy K et al. 2021. "Designing P. aeruginosa synthetic phages with reduced genomes." Scientific Reports, 11 (1).
Version
Final published version
Abstract
© 2021, The Author(s). In the era where antibiotic resistance is considered one of the major worldwide concerns, bacteriophages have emerged as a promising therapeutic approach to deal with this problem. Genetically engineered bacteriophages can enable enhanced anti-bacterial functionalities, but require cloning additional genes into the phage genomes, which might be challenging due to the DNA encapsulation capacity of a phage. To tackle this issue, we designed and assembled for the first time synthetic phages with smaller genomes by knocking out up to 48% of the genes encoding hypothetical proteins from the genome of the newly isolated Pseudomonas aeruginosa phage vB_PaeP_PE3. The antibacterial efficacy of the wild-type and the synthetic phages was assessed in vitro as well as in vivo using a Galleria mellonella infection model. Overall, both in vitro and in vivo studies revealed that the knock-outs made in phage genome do not impair the antibacterial properties of the synthetic phages, indicating that this could be a good strategy to clear space from phage genomes in order to enable the introduction of other genes of interest that can potentiate the future treatment of P. aeruginosa infections.
MIT Department
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Synthetic Biology Center
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/S41598-021-81580-2
