RT Journal Article
T1 Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms
A1 Mazzolini, Rocco
A1 Rodríguez Arce, Irene
A1 Fernández Barat, Laia
A1 Piñero Lambea, Carlos
A1 Garrido, Victoria
A1 Rebollada Merino, Agustín Miguel
A1 Motos, Anna
A1 Torres, Antoni
A1 Grilló, Maria Jesús
A1 Serrano, Luis
A1 Lluch Senar, Maria
AB 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.
SN 1087-0156
SN 1546-1696
YR 2023
FD 2023-01-19
LK https://hdl.handle.net/20.500.14352/107485
UL https://hdl.handle.net/20.500.14352/107485
LA eng
NO Mazzolini, R., Rodríguez-Arce, I., Fernández-Barat, L., Piñero-Lambea, C., Garrido, V., Rebollada-Merino, A., Motos, A., Torres, A., Grilló, M. J., Serrano, L., & Lluch-Senar, M. (2023). Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms. Nature biotechnology, 41(8), 1089–1098. https://doi.org/10.1038/s41587-022-01584-9
NO Online contentAny methods, additional references, Nature Portfolio reporting summaries, source data, extended data, supplementary information, acknowledgements, peer review information; details of author contributions and competing interests; and statements of data and code availability are available at https://doi.org/10.1038/s41587-022-01584-9.Author contributionsR.M. and I.R.-A. designed and performed experiments, analyzed data and wrote the paper. L.F.-B., C.P.-L. and V.G. designed and performed experiments. A.R.-M. and A.M. analyzed data. A.T. and M.J.-G. gave technical support and conceptual advice. L.S. and M.L.-S. designed experiments, analyzed data, gave technical support and conceptual advice, wrote the paper and led the project.Competing interestsThe results published in this article are covered by patents US10745450B2, EP3262061A1 and PCT/EP2021/057122 (licensed to Pulmobiotics S.L) and PCT/EP2021/059142. L.S. and M.L. are shareholders of Pulmobiotics S.L..R.M., C.P. and M.L. are employees and have stock options of Pulmobiotics S.L. The remaining authors declare no competing interests.
DS Docta Complutense
RD 12 abr 2025