Engineering a genome-reduced bacterium to eliminate Staphylococcus aureus biofilms in vivo
Autor/a
Garcia-Ramallo Pla, EVA
Gallo, Carolina
Peñuelas, Ivan
Serrano, Luis
Fecha de publicación
2021ISSN
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
English
Materias (CDU)
57 - Biología
578 - Virología
616.9 - Enfermedades infecciosas y contagiosas. Fiebres
Palabras clave
Bacteris
Genoma
Staphylococcus aureus
Bacterias
Genoma
Staphylococcus aureus
Bacteria
Genome
Staphylococcus aureus
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: 16 dic. 2021. DOI: 10.15252/msb.202010145
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Derechos
2021 - The Authors. Published under the terms of the CC BY4.0 license.
Excepto si se señala otra cosa, la licencia del ítem se describe como https://creativecommons.org/licenses/by/4.0/