Design of live attenuated bacterial vaccines based on D-glutamate auxotrophy
| UDC.coleccion | Investigación | es_ES |
| UDC.departamento | Fisioterapia, Medicina e Ciencias Biomédicas | es_ES |
| UDC.grupoInv | Investigación en Microbiología (INIBIC) | es_ES |
| UDC.institutoCentro | INIBIC - Instituto de Investigacións Biomédicas de A Coruña | es_ES |
| UDC.issue | 15480 | es_ES |
| UDC.journalTitle | Nature Communications | es_ES |
| UDC.volume | 8 | es_ES |
| dc.contributor.author | Cabral, M. P. | |
| dc.contributor.author | García, Patricia | |
| dc.contributor.author | Beceiro Casas, Alejandro | |
| dc.contributor.author | Rumbo, Carlos | |
| dc.contributor.author | Pérez Gómez, Astrid | |
| dc.contributor.author | Moscoso, Miriam | |
| dc.contributor.author | Bou, Germán | |
| dc.date.accessioned | 2025-03-27T12:43:57Z | |
| dc.date.available | 2025-03-27T12:43:57Z | |
| dc.date.issued | 2017-05-26 | |
| dc.description.abstract | [Abstract] Vaccine development is a priority for global health due to the growing multidrug resistance in bacteria. D-glutamate synthesis is essential for bacterial cell wall formation. Here we present a strategy for generating effective bacterial whole-cell vaccines auxotrophic for D-glutamate. We apply this strategy to generate D-glutamate auxotrophic vaccines for three major pathogens, Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureus. These bacterial vaccines show virulence attenuation and self-limited growth in mice, and elicit functional and cross-reactive antibodies, and cellular immunity. These responses correlate with protection against acute lethal infection with other strains of the same species, including multidrug resistant, virulent and/or high-risk clones such as A. baumannii AbH12O-A2 and Ab307-0294, P. aeruginosa PA14, and community-acquired methicillin-resistant S. aureus USA300LAC. This approach can potentially be applied for the development of live-attenuated vaccines for virtually any other bacterial pathogens, and does not require the identification of virulence determinants, which are often pathogen-specific. | es_ES |
| dc.description.sponsorship | This work was funded by the Projects PI12/00552 and PI15/00860, integrated in the National Plan for Scientific Research, Development and Technological Innovation 2013–2016 and funded by the Instituto de Salud Carlos III (ISCIII) and Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD12/0015/0014 and REIPI RD16/0016/0006)—co-financed by European Development Regional Fund ERDF ‘A way to achieve Europe’, Operative program Intelligent Growth 2014–2020. This work was also supported by the program ‘Innova Saúde’ implemented by SERGAS-Galician Healthcare Service. MPC was supported by a PhD scholarship (SFRH/BD/64740/2009) from Portugal and POPH/FSE. PG was supported by the Spanish Network for Research in Infectious Diseases (REIPI RD12/0015/0014 and RD16/0016/0006). AB was supported by the Miguel Servet Programme CP13/00226. AP was supported by the Galician Plan for Research, Innovation and Growth (I2C Plan, 2011–2015). We are grateful to S. Rodríguez and M. Fernández for technical assistance. C. Juan (Hospital Universitario Son Espases) for technical advice, B. Fernández for the provision of clinical P. aeruginosa and S. aureus strains (University Hospital A Coruña), D. Velasco and L.P. Barbeyto for the provision of clinical CoN-Staphylococci strains, T. Russo (The University at Buffalo-State University of New York) for Ab307-0294, C. Winstanley (University of Liverpool) for LES400 and LES431, J. Blázquez (IBIS-University Hospital Virgen del Rocío)) for PA14, F. Chaves (Hospital 12 de Octubre) for PA21_ST175, C. Peña (Hospital Universitari de Bellvitge) for PA_ST235, M. Rodicio (Universidad de Oviedo) and L. Cavaco (Technical University of Denmark) for RN4220, T. Foster (Trinity College) for DH10β, F. DeLeo (National Institute of Allergy and Infectious Diseases, USA) for FPR3757-USA300LAC and for MW2, T. Baba (Juntendo University) for NEWMAN, R. Fitzgerald (Trinity College) for RF122, ED133 and ED98, M. Voskuil (University of Colorado School of Medicine) for pMo130, H. Schweizer (Colorado State University) for pEX18Gm and I. Lasa (Instituto de Agrobiotecnologia—CSIC—Universidad Pública de Navarra) for S. aureus 132, 132 Δspa and pMAD. | es_ES |
| dc.description.sponsorship | info:eu-repo/grantAgreement/MINECO/Acción Estratégica de Salud/PI12%2F00552/ES/Estudios preclínicos con D-aminoácidos para atenuar la virulencia de Acinetobacter baumannii y otros patógenos multirresistentes: Una nueva estrategia para erradicar una infección | es_ES |
| dc.description.sponsorship | info:eu-repo/grantAgreement/MINECO/Programa Estatal de I+D+I Orientada a los Retos de la Sociedad/PI15%2F00860/ES/Desarrollo de una plataforma universal de vacunas bacterianas vivas atenuadas auxótrofas para D-glutamato: prevención y erradicación de infecciones por bacterias multirresistentes | es_ES |
| dc.description.sponsorship | info:eu-repo/grantAgreement/MINECO/Acción Estratégica de Salud/RD12%2F0015%2F0014/ES/Enfermedades infecciosas | es_ES |
| dc.description.sponsorship | info:eu-repo/grantAgreement/MINECO/Programa Estatal de I+D+I Orientada a los Retos de la Sociedad/RD16%2F0016%2F0006/ES/RED ESPAÑOLA DE INVESTIGACIÓN EN PATOLOGÍAS INFECCIOSAS | es_ES |
| dc.identifier.citation | Cabral MP, García P, Beceiro A, Rumbo C, Pérez A, Moscoso M, Bou G. Design of live attenuated bacterial vaccines based on D-glutamate auxotrophy. Nat Commun. 2017 May 26;8:15480. | es_ES |
| dc.identifier.doi | 10.1038/ncomms15480 | |
| dc.identifier.issn | 2041-1723 | |
| dc.identifier.uri | http://hdl.handle.net/2183/41566 | |
| dc.language.iso | eng | es_ES |
| dc.publisher | Springer Nature | es_ES |
| dc.relation.uri | https://doi.org/10.1038/ncomms15480 | es_ES |
| dc.rights | Creative Commons Attribution 4.0 International License (CC-BY 4.0) | es_ES |
| dc.rights.accessRights | open access | es_ES |
| dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
| dc.subject | Bacteria | es_ES |
| dc.subject | Bacterial infections | es_ES |
| dc.subject | Bacterial vaccines | es_ES |
| dc.subject | Glutamic acid | es_ES |
| dc.subject | Vaccines, Attenuated | es_ES |
| dc.title | Design of live attenuated bacterial vaccines based on D-glutamate auxotrophy | es_ES |
| dc.type | journal article | es_ES |
| dc.type.hasVersion | VoR | es_ES |
| dspace.entity.type | Publication | |
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