Journal
NATURE COMMUNICATIONS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms15480
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Funding
- National Plan for Scientific Research, Development and Technological Innovation [PI12/00552, PI15/00860]
- Instituto de Salud Carlos III (ISCIII)
- Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Economia, Industria y Competitividad, Spanish Network for Research in Infectious Diseases by European Development Regional Fund ERDF 'A way to achieve Europe' [REIPI RD12/0015/0014, REIPI RD16/0016/0006]
- program 'Innova Saude' by SERGAS-Galician Healthcare Service
- PhD scholarship from Portugal [SFRH/BD/64740/2009]
- POPH/FSE
- Spanish Network for Research in Infectious Diseases [REIPI RD12/0015/0014, RD16/ 0016/0006]
- Miguel Servet Programme [CP13/00226]
- Galician Plan for Research, Innovation and Growth (I2C Plan)
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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.
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