Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms

Engineered live bacteria could provide a new modality for treating lung infections, a major cause of mortality worldwide. In the present study, we engineered a genome-reduced human lung bacterium, Mycoplasma pneumoniae, to treat ventilator-associated pneumonia, a disease with high hospital mortality...

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Autores: Mazzolini, Rocco, Rodríguez-Arce, Irene, Fernández-Barat, Laia, Piñero-Lambea, Carlos, Garrido, Victoria, Rebollada-Merino, Agustín, Motos, Ana, Torres, Antoni, Grilló, María-Jesús, Serrano Pubull, Luis, 1982-, Lluch-Senar, Maria 1982-
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/55842
Acceso en línea:http://hdl.handle.net/10230/55842
http://dx.doi.org/10.1038/s41587-022-01584-9
Access Level:acceso abierto
Palabra clave:Biotechnology
Synthetic biology
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network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms
title Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms
spellingShingle Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms
Mazzolini, Rocco
Biotechnology
Synthetic biology
title_short Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms
title_full Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms
title_fullStr Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms
title_full_unstemmed Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms
title_sort Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms
dc.creator.none.fl_str_mv Mazzolini, Rocco
Rodríguez-Arce, Irene
Fernández-Barat, Laia
Piñero-Lambea, Carlos
Garrido, Victoria
Rebollada-Merino, Agustín
Motos, Ana
Torres, Antoni
Grilló, María-Jesús
Serrano Pubull, Luis, 1982-
Lluch-Senar, Maria 1982-
author Mazzolini, Rocco
author_facet Mazzolini, Rocco
Rodríguez-Arce, Irene
Fernández-Barat, Laia
Piñero-Lambea, Carlos
Garrido, Victoria
Rebollada-Merino, Agustín
Motos, Ana
Torres, Antoni
Grilló, María-Jesús
Serrano Pubull, Luis, 1982-
Lluch-Senar, Maria 1982-
author_role author
author2 Rodríguez-Arce, Irene
Fernández-Barat, Laia
Piñero-Lambea, Carlos
Garrido, Victoria
Rebollada-Merino, Agustín
Motos, Ana
Torres, Antoni
Grilló, María-Jesús
Serrano Pubull, Luis, 1982-
Lluch-Senar, Maria 1982-
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Biotechnology
Synthetic biology
topic Biotechnology
Synthetic biology
description Engineered live bacteria could provide a new modality for treating lung infections, a major cause of mortality worldwide. In the present study, we engineered a genome-reduced human lung bacterium, Mycoplasma pneumoniae, to treat ventilator-associated pneumonia, a disease with high hospital mortality when associated with Pseudomonas aeruginosa biofilms. After validating the biosafety of an attenuated M. pneumoniae chassis in mice, we introduced four transgenes into the chromosome by transposition to implement bactericidal and biofilm degradation activities. We show that this engineered strain has high efficacy against an acute P. aeruginosa lung infection in a mouse model. In addition, we demonstrated that the engineered strain could dissolve biofilms formed in endotracheal tubes of patients with ventilator-associated pneumonia and be combined with antibiotics targeting the peptidoglycan layer to increase efficacy against Gram-positive and Gram-negative bacteria. We expect our M. pneumoniae-engineered strain to be able to treat biofilm-associated infections in the respiratory tract.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/55842
http://dx.doi.org/10.1038/s41587-022-01584-9
url http://hdl.handle.net/10230/55842
http://dx.doi.org/10.1038/s41587-022-01584-9
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nat Biotechnol. 2023 Aug;41(8):1089-98
info:eu-repo/grantAgreement/EC/H2020/670216
info:eu-repo/grantAgreement/EC/H2020/634942
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
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spelling Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilmsMazzolini, RoccoRodríguez-Arce, IreneFernández-Barat, LaiaPiñero-Lambea, CarlosGarrido, VictoriaRebollada-Merino, AgustínMotos, AnaTorres, AntoniGrilló, María-JesúsSerrano Pubull, Luis, 1982-Lluch-Senar, Maria 1982-BiotechnologySynthetic biologyEngineered live bacteria could provide a new modality for treating lung infections, a major cause of mortality worldwide. In the present study, we engineered a genome-reduced human lung bacterium, Mycoplasma pneumoniae, to treat ventilator-associated pneumonia, a disease with high hospital mortality when associated with Pseudomonas aeruginosa biofilms. After validating the biosafety of an attenuated M. pneumoniae chassis in mice, we introduced four transgenes into the chromosome by transposition to implement bactericidal and biofilm degradation activities. We show that this engineered strain has high efficacy against an acute P. aeruginosa lung infection in a mouse model. In addition, we demonstrated that the engineered strain could dissolve biofilms formed in endotracheal tubes of patients with ventilator-associated pneumonia and be combined with antibiotics targeting the peptidoglycan layer to increase efficacy against Gram-positive and Gram-negative bacteria. We expect our M. pneumoniae-engineered strain to be able to treat biofilm-associated infections in the respiratory tract.This work was supported by the European Research Council under the European Union’s Horizon 2020 research and innovation program, under grant agreement no. 670216 (MYCOCHASSIS). We thank the Spanish Ministry of Economy, Industry and Competitiveness to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the CERCA Program from the Generalitat de Catalunya, the European Union’s Horizon 2020 Research and Innovation Programme, grant no. 634942 (MycoSynVac), La Caixa Health (HR18-00058), CB 06/06/0028/CIBER de enfermedades respiratorias-Ciberes and ICREA Academy/Institució Catalana de Recerca i Estudis Avançats, 2.603/IDIBAPS, SGR/Generalitat de Catalunya for their support. M.L.-S. thanks the funder Instituto de Salud Carlos III (ISCIII, Acción Estratégica en Salud 2016, FEDER project, reference CP16/00094) for support of the research of this work. We also thank the staff of the CRG/UPF Proteomics Unit, which is part of the Spanish Infrastructure for Omics Technologies unit and a member of the ProteoRed PRB3 consortium, supported by grant no. PT17/0019 of the PE I+D+i 2013–2016 from the ISCIII and European Regional Development Fund.Nature Research202320232023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/55842http://dx.doi.org/10.1038/s41587-022-01584-9reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésNat Biotechnol. 2023 Aug;41(8):1089-98info:eu-repo/grantAgreement/EC/H2020/670216info:eu-repo/grantAgreement/EC/H2020/634942© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/558422026-05-29T05:05:01Z
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