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

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  • dc.contributor.author Mazzolini, Rocco
  • dc.contributor.author Rodríguez-Arce, Irene
  • dc.contributor.author Fernández-Barat, Laia
  • dc.contributor.author Piñero-Lambea, Carlos
  • dc.contributor.author Garrido, Victoria
  • dc.contributor.author Rebollada-Merino, Agustín
  • dc.contributor.author Motos, Ana
  • dc.contributor.author Torres, Antoni
  • dc.contributor.author Grilló, María-Jesús
  • dc.contributor.author Serrano Pubull, Luis, 1982-
  • dc.contributor.author Lluch-Senar, Maria 1982-
  • dc.date.accessioned 2023-02-22T07:21:56Z
  • dc.date.available 2023-02-22T07:21:56Z
  • dc.date.issued 2023
  • dc.description.abstract 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.
  • dc.description.sponsorship 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.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Mazzolini R, Rodríguez-Arce I, Fernández-Barat L, Piñero-Lambea C, Garrido V, Rebollada-Merino A, Motos A, Torres A, Grilló MJ, Serrano L, Lluch-Senar M. Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms. Nat Biotechnol. 2023 Aug;41(8):1089-98. DOI: 10.1038/s41587-022-01584-9
  • dc.identifier.doi http://dx.doi.org/10.1038/s41587-022-01584-9
  • dc.identifier.issn 1087-0156
  • dc.identifier.uri http://hdl.handle.net/10230/55842
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Nat Biotechnol. 2023 Aug;41(8):1089-98
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/670216
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/634942
  • dc.rights © 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/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Biotechnology
  • dc.subject.keyword Synthetic biology
  • dc.title Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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