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

Garrido, Victoria; Piñero-Lambea, Carlos; Rodriguez-Arce, Irene; Paetzold, Bernhard, 1981-; Ferrar, Tony; Weber, Marc; Garcia Ramallo, Eva; Gallo López, Carolina, 1984-; Collantes, María; Peñuelas, Iván; Serrano Pubull, Luis, 1982-; Grilló, María-Jesús; Lluch-Senar, Maria 1982-

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

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dc.contributor.author Garrido, Victoria
dc.contributor.author Piñero-Lambea, Carlos
dc.contributor.author Rodriguez-Arce, Irene
dc.contributor.author Paetzold, Bernhard, 1981-
dc.contributor.author Ferrar, Tony
dc.contributor.author Weber, Marc
dc.contributor.author Garcia Ramallo, Eva
dc.contributor.author Gallo López, Carolina, 1984-
dc.contributor.author Collantes, María
dc.contributor.author Peñuelas, Iván
dc.contributor.author Serrano Pubull, Luis, 1982-
dc.contributor.author Grilló, María-Jesús
dc.contributor.author Lluch-Senar, Maria 1982-
dc.date.accessioned 2022-01-25T11:46:46Z
dc.date.available 2022-01-25T11:46:46Z
dc.date.issued 2021
dc.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.
dc.description.sponsorship This work has been supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program, under grant agreement 670216 (MYCOCHASSIS). We also acknowledge the support of the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership, the Centro de Excelencia Severo Ochoa, the CERCA Program from the Generalitat de Catalunya, the European Union’s Horizon 2020 research and innovation program under grant agreement 634942 (MycoSynVac), and the La Caixa Fundation grant (Livetherapeutics HR18-00058). M.L.-S. acknowledges the support from FEDER project from Instituto Carlos III (ISCIII, Acción Estratégica en Salud 2016) (reference CP16/00094). We also acknowledge the staff of CRG/UPF Proteomics Unit, which is part of the Spanish Infrastructure for Omics Technologies (ICTS OmicsTech) unit is a member of the ProteoRed PRB3 consortium, which is supported by grant PT17/0019 of the PE I + D+i 2013-2016 from the Instituto de Salud Carlos III (ISCIII) and ERDF
dc.format.mimetype application/pdf
dc.identifier.citation Garrido V, Piñero-Lambea C, Rodriguez-Arce I, Paetzold B, Ferrar T, Weber M et al. Engineering a genome-reduced bacterium to eliminate Staphylococcus aureus biofilms in vivo. Mol Syst Biol. 2021 Oct;17(10):e10145. DOI: 10.15252/msb.202010145
dc.identifier.doi http://dx.doi.org/10.15252/msb.202010145
dc.identifier.issn 1744-4292
dc.identifier.uri http://hdl.handle.net/10230/52317
dc.language.iso eng
dc.publisher Wiley Open Access
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/670216
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/634942
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by/4.0/deed.ca
dc.subject.other Bacteris -- Tractament
dc.subject.other Home -- Malalties
dc.subject.other Micoplasmosis
dc.subject.other Genòmica
dc.title Engineering a genome-reduced bacterium to eliminate Staphylococcus aureus biofilms in vivo
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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