Engineering a genome-reduced bacterium to eliminate Staphylococcus aureus biofilms in vivo
Autor/a
Garcia-Ramallo Pla, EVA
Gallo, Carolina
Peñuelas, Ivan
Serrano, Luis
Data de publicació
2021ISSN
1744-4292
Resum
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.
Tipus de document
Article
Versió del document
Versió publicada
Llengua
English
Matèries (CDU)
57 - Biologia
578 - Virologia
616.9 - Malalties infeccioses i contagioses. Febres
Paraules clau
Bacteris
Genoma
Staphylococcus aureus
Bacterias
Genoma
Staphylococcus aureus
Bacteria
Genome
Staphylococcus aureus
Pàgines
20
Publicat per
EMBO Press
Col·lecció
17;
Publicat a
Molecular Systems Biology
Citació
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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- Ciències Bàsiques [65]
Drets
2021 - The Authors. Published under the terms of the CC BY4.0 license.
Excepte que s'indiqui una altra cosa, la llicència de l'ítem es descriu com https://creativecommons.org/licenses/by/4.0/