Engineering a genome‐reduced bacterium to eliminate Staphylococcus aureus biofilms in vivo

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 tra...

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Autores principales:	Victoria Garrido, Carlos Piñero‐Lambea, Irene Rodriguez‐Arce, Bernhard Paetzold, Tony Ferrar, Marc Weber, Eva Garcia‐Ramallo, Carolina Gallo, María Collantes, Iván Peñuelas, Luis Serrano, María‐Jesús Grilló, María Lluch‐Senar
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	bacterial therapy biofilm in vivo Mycoplasma synthetic biology Biology (General) QH301-705.5 Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e81cf3839c824b17817201e7486d0d94
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spelling	oai:doaj.org-article:e81cf3839c824b17817201e7486d0d942021-11-11T11:30:47ZEngineering a genome‐reduced bacterium to eliminate Staphylococcus aureus biofilms in vivo1744-429210.15252/msb.202010145https://doaj.org/article/e81cf3839c824b17817201e7486d0d942021-10-01T00:00:00Zhttps://doi.org/10.15252/msb.202010145https://doaj.org/toc/1744-4292Abstract 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.Victoria GarridoCarlos Piñero‐LambeaIrene Rodriguez‐ArceBernhard PaetzoldTony FerrarMarc WeberEva Garcia‐RamalloCarolina GalloMaría CollantesIván PeñuelasLuis SerranoMaría‐Jesús GrillóMaría Lluch‐SenarWileyarticlebacterial therapybiofilmin vivoMycoplasmasynthetic biologyBiology (General)QH301-705.5Medicine (General)R5-920ENMolecular Systems Biology, Vol 17, Iss 10, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bacterial therapy biofilm in vivo Mycoplasma synthetic biology Biology (General) QH301-705.5 Medicine (General) R5-920
spellingShingle	bacterial therapy biofilm in vivo Mycoplasma synthetic biology Biology (General) QH301-705.5 Medicine (General) R5-920 Victoria Garrido Carlos Piñero‐Lambea Irene Rodriguez‐Arce Bernhard Paetzold Tony Ferrar Marc Weber Eva Garcia‐Ramallo Carolina Gallo María Collantes Iván Peñuelas Luis Serrano María‐Jesús Grilló María Lluch‐Senar Engineering a genome‐reduced bacterium to eliminate Staphylococcus aureus biofilms in vivo
description	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.
format	article
author	Victoria Garrido Carlos Piñero‐Lambea Irene Rodriguez‐Arce Bernhard Paetzold Tony Ferrar Marc Weber Eva Garcia‐Ramallo Carolina Gallo María Collantes Iván Peñuelas Luis Serrano María‐Jesús Grilló María Lluch‐Senar
author_facet	Victoria Garrido Carlos Piñero‐Lambea Irene Rodriguez‐Arce Bernhard Paetzold Tony Ferrar Marc Weber Eva Garcia‐Ramallo Carolina Gallo María Collantes Iván Peñuelas Luis Serrano María‐Jesús Grilló María Lluch‐Senar
author_sort	Victoria Garrido
title	Engineering a genome‐reduced bacterium to eliminate Staphylococcus aureus biofilms in vivo
title_short	Engineering a genome‐reduced bacterium to eliminate Staphylococcus aureus biofilms in vivo
title_full	Engineering a genome‐reduced bacterium to eliminate Staphylococcus aureus biofilms in vivo
title_fullStr	Engineering a genome‐reduced bacterium to eliminate Staphylococcus aureus biofilms in vivo
title_full_unstemmed	Engineering a genome‐reduced bacterium to eliminate Staphylococcus aureus biofilms in vivo
title_sort	engineering a genome‐reduced bacterium to eliminate staphylococcus aureus biofilms in vivo
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/e81cf3839c824b17817201e7486d0d94
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Engineering a genome‐reduced bacterium to eliminate Staphylococcus aureus biofilms in vivo

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