Engineering a genome reduced bacterium to eliminate Staphylococcus aureus biofilms in vivo
Author
Garcia Ramallo, Eva
Serrano, Luis
Publication date
2021DOI
10.15252/msb.202010145
ISSN
1744-4292
Abstract
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.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
61 - Medical sciences
Keywords
Teràpia bacteriana
Biofilm
In vivo
Mycoplasma
Biologia sintètica
Terapia bacteriana
Biopelícula
In vivo
Micoplasma
Biología sintética
Bacterial therapy
Biofilm
In vivo
Mycoplasma
Synthetic biology
Pages
20
Publisher
EMBO Press
Collection
17
Is part of
Molecular Systems Biology
Citation
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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- Ciències Bàsiques [65]
Rights
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/deed.es