Cabral, M. P.García, PatriciaBeceiro Casas, AlejandroRumbo, CarlosPérez Gómez, AstridMoscoso, MiriamBou, Germán2025-03-272025-03-272017-05-26Cabral 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;8:15480.2041-1723http://hdl.handle.net/2183/41566[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.engCreative Commons Attribution 4.0 International License (CC-BY 4.0)http://creativecommons.org/licenses/by/3.0/es/BacteriaBacterial infectionsBacterial vaccinesGlutamic acidVaccines, Attenuatedjournal articleopen access10.1038/ncomms15480