Mazzolini, RoccoRodríguez-Arce, IreneFernández-Barat, LaiaPiñero-Lambea, CarlosGarrido, VictoriaRebollada-Merino, AgustínMotos, AnaTorres, AntoniGrilló, María-JesúsSerrano Pubull, Luis, 1982-Lluch-Senar, Maria 1982-2023-02-222023-02-222023Mazzolini 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/s41587-022-01584-91087-0156http://hdl.handle.net/10230/55842Engineered 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.application/pdfeng© 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/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41587-022-01584-9BiotechnologySynthetic biologyinfo:eu-repo/semantics/openAccess