Engineering a genome reduced bacterium to eliminate Staphylococcus aureus biofilms in vivo
Autor/a
Garcia Ramallo, Eva
Serrano, Luis
Fecha de publicación
2021DOI
10.15252/msb.202010145
ISSN
1744-4292
Resumen
Bacteria present a promising delivery system for treating human diseases. Here, we engineered the genome-reduced human lung pathogen Mycoplasma pneumoniae as a live biotherapeutic to treat biofilm-associated bacterial infections. This strain has a unique genetic code, which hinders gene transfer to most other bacterial genera, and it lacks a cell wall, which allows it to express proteins that target peptidoglycans of pathogenic bacteria. We first determined that removal of the pathogenic factors fully attenuated the chassis strain in vivo. We then designed synthetic promoters and identified an endogenous peptide signal sequence that, when fused to heterologous proteins, promotes efficient secretion. Based on this, we equipped the chassis strain with a genetic platform designed to secrete antibiofilm and bactericidal enzymes, resulting in a strain capable of dissolving Staphylococcus aureus biofilms preformed on catheters in vitro, ex vivo, and in vivo. To our knowledge, this is the first engineered genome-reduced bacterium that can fight against clinically relevant biofilm-associated bacterial infections.
Tipo de documento
Artículo
Versión del documento
Versión publicada
Lengua
Inglés
Materias (CDU)
61 - Medicina
Palabras clave
Teràpia bacteriana
Biofilm
In vivo
Mycoplasma
Biologia sintètica
Terapia bacteriana
Biopelícula
In vivo
Micoplasma
Biología sintética
Bacterial therapy
Biofilm
In vivo
Mycoplasma
Synthetic biology
Páginas
20
Publicado por
EMBO Press
Colección
17
Publicado en
Molecular Systems Biology
Citación
Garrido, Victoria; Piñero Lambea, Carlos; Rodriguez Arce, Irene [et al.]. Engineering a genome-reduced bacterium to eliminate Staphylococcus aureus biofilms in vivo. Molecular Systems Biology, 2021, 17, e10145. Disponible en: <https://www.embopress.org/doi/full/10.15252/msb.202010145>. Fecha de acceso: 6 jun. 2023. DOI: 10.15252/msb.202010145
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