Proteomics

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Engineered live bacteria suppress Pseudomonas aeruginosa lung infection in mouse and dissolve biofilm in endotracheal tubes from patients


ABSTRACT: Engineered live bacteria could provide a new modality for treating lung infections , a major cause of mortality worldwide. Here, we engineered a genome-reduced human lung bacterium, Mycoplasma pneumoniae, to treat ventilator-associated pneumonia (VAP), 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 in 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 demonstrate that the engineered strain can dissolve biofilms formed in endotracheal tubes of VAP patients and can be combined with antibiotics targeting the peptidoglycan layer to increase efficacy against gram-positive and gram-negative bacteria. We expect that our

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mycoplasma Pneumoniae (strain Atcc 29342 / M129)

SUBMITTER: Rocco Mazzolini  

LAB HEAD: Maria Lluch-Senar

PROVIDER: PXD037233 | Pride | 2023-10-24

REPOSITORIES: Pride

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

Mazzolini Rocco R   Rodríguez-Arce Irene I   Fernández-Barat Laia L   Piñero-Lambea Carlos C   Garrido Victoria V   Rebollada-Merino Agustín A   Motos Anna A   Torres Antoni A   Grilló Maria Jesús MJ   Serrano Luis L   Lluch-Senar Maria M  

Nature biotechnology 20230119 8


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  ...[more]

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