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

Investigation published in Nature Biotechnology

January 19th, 2023

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




Mazzolini R., Rodriguez-Arce I., Fernandez-Barat L., Pinero-Lambea C., Garrido V., Rebollada A., Motos A., Torres A., Grillo MJ., Serrano L. and Lluch-Senar M.




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

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



Participants:

Centre for Genomic Regulation. Barcelona Institute of Science and Technology.

Pulmobiotics Ltd.

Gobierno de NavarraInstituto de Agrobiotecnologia. Gobierno de Navarra.

Universitat de BarcelonaCellex Laboratory, CibeRes. Institut d’Investigacions Biomèdiques August Pi i Sunyer. Universitat de Barcelona (UB).

Department of Pneumology. Thorax Institute. Hospital Clinic of Barcelona.

Universidad ComplutenseServicio de Patología y Veterinaria Forense (SAP). Centro de Vigilancia Sanitaria Veterinaria (VISAVET). Universidad Complutense (UCM).

Universidad ComplutenseDepartamento de Medicina y Cirugía Animal. Facultad de Veterinaria. Universidad Complutense (UCM).

Universitat Pompeu Fabra.

ICREA.

Basic Sciences Department. Faculty of Medicine and Health Sciences. Universitat Internacional de Catalunya.







FACTOR YEAR Q
68.164 2021

NLMID: -150

PMID: 36658340

ISSN: 1087-0156



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


JOURNAL: Nat. Biotechnol


AÑO: 2023


PUBLISHER: Nature Portfolio


AUTHORS: Mazzolini R., Rodriguez-Arce I., Fernandez-Barat L., Pinero-Lambea C., Garrido V., Rebollada A., Motos A., Torres A., Grillo MJ., Serrano L. and Lluch-Senar M.


VISAVET PARTICIPANTS


Agustín Miguel Rebollada Merino

DOI: https://doi.org/10.1038/s41587-022-01584-9


CITE THIS PUBLICATION:

Mazzolini R., Rodriguez-Arce I., Fernandez-Barat L., Pinero-Lambea C., Garrido V., Rebollada A., Motos A., Torres A., Grillo MJ., Serrano L. and Lluch-Senar M. Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms. Nature Biotechnology. 2023. (A). ISSN: 1087-0156. DOI: 10.1038/s41587-022-01584-9


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