Designing P. aeruginosa synthetic phages with reduced genomes

Abstract 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...

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Autores principales:	Diana P. Pires, Rodrigo Monteiro, Dalila Mil-Homens, Arsénio Fialho, Timothy K. Lu, Joana Azeredo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ae5ac1d34e5c4cd7b8a8b178354b4d5a
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spelling	oai:doaj.org-article:ae5ac1d34e5c4cd7b8a8b178354b4d5a2021-12-02T14:16:42ZDesigning P. aeruginosa synthetic phages with reduced genomes10.1038/s41598-021-81580-22045-2322https://doaj.org/article/ae5ac1d34e5c4cd7b8a8b178354b4d5a2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81580-2https://doaj.org/toc/2045-2322Abstract 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.Diana P. PiresRodrigo MonteiroDalila Mil-HomensArsénio FialhoTimothy K. LuJoana AzeredoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Diana P. Pires Rodrigo Monteiro Dalila Mil-Homens Arsénio Fialho Timothy K. Lu Joana Azeredo Designing P. aeruginosa synthetic phages with reduced genomes
description	Abstract 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.
format	article
author	Diana P. Pires Rodrigo Monteiro Dalila Mil-Homens Arsénio Fialho Timothy K. Lu Joana Azeredo
author_facet	Diana P. Pires Rodrigo Monteiro Dalila Mil-Homens Arsénio Fialho Timothy K. Lu Joana Azeredo
author_sort	Diana P. Pires
title	Designing P. aeruginosa synthetic phages with reduced genomes
title_short	Designing P. aeruginosa synthetic phages with reduced genomes
title_full	Designing P. aeruginosa synthetic phages with reduced genomes
title_fullStr	Designing P. aeruginosa synthetic phages with reduced genomes
title_full_unstemmed	Designing P. aeruginosa synthetic phages with reduced genomes
title_sort	designing p. aeruginosa synthetic phages with reduced genomes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ae5ac1d34e5c4cd7b8a8b178354b4d5a
work_keys_str_mv	AT dianappires designingpaeruginosasyntheticphageswithreducedgenomes AT rodrigomonteiro designingpaeruginosasyntheticphageswithreducedgenomes AT dalilamilhomens designingpaeruginosasyntheticphageswithreducedgenomes AT arseniofialho designingpaeruginosasyntheticphageswithreducedgenomes AT timothyklu designingpaeruginosasyntheticphageswithreducedgenomes AT joanaazeredo designingpaeruginosasyntheticphageswithreducedgenomes
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Designing P. aeruginosa synthetic phages with reduced genomes

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