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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| Format: | Article |
| Language: | English |
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Springer Nature
2021-10-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.202010145 |
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| 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 |
| collection | DOAJ |
| 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 |
| id | doaj-art-e81cf3839c824b17817201e7486d0d94 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2021-10-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-e81cf3839c824b17817201e7486d0d942025-08-20T03:42:04ZengSpringer NatureMolecular Systems Biology1744-42922021-10-01171012010.15252/msb.202010145Engineering a genome‐reduced bacterium to eliminate Staphylococcus aureus biofilms in vivoVictoria Garrido0Carlos Piñero‐Lambea1Irene Rodriguez‐Arce2Bernhard Paetzold3Tony Ferrar4Marc Weber5Eva Garcia‐Ramallo6Carolina Gallo7María Collantes8Iván Peñuelas9Luis Serrano10María‐Jesús Grilló11María Lluch‐Senar12Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyRADIOMIN Research Group, Clínica Universidad de NavarraRADIOMIN Research Group, Clínica Universidad de NavarraCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyInstitute of Agrobiotechnology (IdAB; CSIC‐Navarra Government)Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyAbstract 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.https://doi.org/10.15252/msb.202010145bacterial therapybiofilmin vivoMycoplasmasynthetic biology |
| spellingShingle | 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 Molecular Systems Biology bacterial therapy biofilm in vivo Mycoplasma synthetic biology |
| title | 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_short | 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 |
| topic | bacterial therapy biofilm in vivo Mycoplasma synthetic biology |
| url | https://doi.org/10.15252/msb.202010145 |
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