Publicação
Designing P. aeruginosa synthetic phages with reduced genomes
| Resumo: | 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. |
|---|---|
| Autores principais: | Pires, Diana Priscila Penso |
| Outros Autores: | Monteiro, Rodrigo; Mil-Homens, Dalila; Fialho, Arsénio; Lu, Timothy K.; Azeredo, Joana |
| Ano: | 2021 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1867438252213927936 |
|---|---|
| author | Pires, Diana Priscila Penso |
| author2 | Monteiro, Rodrigo Mil-Homens, Dalila Fialho, Arsénio Lu, Timothy K. Azeredo, Joana |
| author2_role | author author author author author |
| author_facet | Pires, Diana Priscila Penso Monteiro, Rodrigo Mil-Homens, Dalila Fialho, Arsénio Lu, Timothy K. Azeredo, Joana |
| author_role | author |
| contributor_name_str_mv | RepositóriUM - Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Pires, Diana Priscila Penso\"},{\"Person.name\":\"Monteiro, Rodrigo\"},{\"Person.name\":\"Mil-Homens, Dalila\"},{\"Person.name\":\"Fialho, Arsénio\"},{\"Person.name\":\"Lu, Timothy K.\"},{\"Person.name\":\"Azeredo, Joana\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | RepositóriUM - Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Pires, Diana Priscila Penso Monteiro, Rodrigo Mil-Homens, Dalila Fialho, Arsénio Lu, Timothy K. Azeredo, Joana |
| datacite.date.Accepted.fl_str_mv | 2021-01-25T00:00:00Z |
| datacite.date.available.fl_str_mv | 2021-02-25T18:33:29Z |
| datacite.date.embargoed.fl_str_mv | 2021-02-25T18:33:29Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.titles.title.fl_str_mv | Designing P. aeruginosa synthetic phages with reduced genomes |
| dc.contributor.none.fl_str_mv | RepositóriUM - Universidade do Minho |
| dc.creator.none.fl_str_mv | Pires, Diana Priscila Penso Monteiro, Rodrigo Mil-Homens, Dalila Fialho, Arsénio Lu, Timothy K. Azeredo, Joana |
| dc.date.Accepted.fl_str_mv | 2021-01-25T00:00:00Z |
| dc.date.available.fl_str_mv | 2021-02-25T18:33:29Z |
| dc.date.embargoed.fl_str_mv | 2021-02-25T18:33:29Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/70438 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Nature Publishing Group |
| dc.rights.cclincense.fl_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.rights.rights.copyright.fl_str_mv | openAccess |
| dc.title.fl_str_mv | Designing P. aeruginosa synthetic phages with reduced genomes |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | 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. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorium.uminho.pt/bitstreams/b2884ace-afa6-452d-96cd-df4cb12b062b/download |
| id | rum_bcbb9c1273e657ea7d5f0fdc1dd942e3 |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/70438 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/70438 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Pires, Diana Priscila Penso Monteiro, Rodrigo Mil-Homens, Dalila Fialho, Arsénio Lu, Timothy K. Azeredo, Joana |
| publishDate | 2021 |
| publisher.none.fl_str_mv | Nature Publishing Group |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engNature Publishing GroupporIn 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.application/pdfporDesigning P. aeruginosa synthetic phages with reduced genomesPires, Diana Priscila PensoMonteiro, RodrigoMil-Homens, DalilaFialho, ArsénioLu, Timothy K.Azeredo, JoanaHostingInstitutionOrganizationalRepositóriUM - Universidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptCITATIONPires, Diana P.; Monteiro, Rodrigo; Mil-Homens, Dalila; Fialho, Arsénio; Lu, Timothy K.; Azeredo, Joana, Designing P. aeruginosa synthetic phages with reduced genomes. Scientific Reports, 11(2164), 2021PMID33495501ISSNIsPartOf2045-2322DOIIsPartOf10.1038/s41598-021-81580-22021-02-25T18:33:29Z2021-01-252021-02-15T16:49:21Z2021-01-25T00:00:00ZHandlehttps://hdl.handle.net/1822/70438http://purl.org/coar/access_right/c_abf2open access2147495 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal article2021-01-25http://creativecommons.org/licenses/by/4.0/openAccesshttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorium.uminho.pt/bitstreams/b2884ace-afa6-452d-96cd-df4cb12b062b/download |
| spellingShingle | Designing P. aeruginosa synthetic phages with reduced genomes Pires, Diana Priscila Penso |
| status | SINGLETON |
| title | 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_short | Designing P. aeruginosa synthetic phages with reduced genomes |
| title_sort | Designing P. aeruginosa synthetic phages with reduced genomes |
| url | https://hdl.handle.net/1822/70438 |
| visible | 1 |