Design of live attenuated bacterial vaccines based on D-glutamate auxotrophy

Maria P. Cabral, Patricia García, Alejandro Beceiro, Carlos Rumbo, Astrid Pérez, Miriam Moscoso and Germán Bou ()
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Maria P. Cabral: University Hospital A Coruña (CHUAC)–Biomedical Research Institute A Coruña (INIBIC)
Patricia García: University Hospital A Coruña (CHUAC)–Biomedical Research Institute A Coruña (INIBIC)
Alejandro Beceiro: University Hospital A Coruña (CHUAC)–Biomedical Research Institute A Coruña (INIBIC)
Carlos Rumbo: University Hospital A Coruña (CHUAC)–Biomedical Research Institute A Coruña (INIBIC)
Astrid Pérez: University Hospital A Coruña (CHUAC)–Biomedical Research Institute A Coruña (INIBIC)
Miriam Moscoso: University Hospital A Coruña (CHUAC)–Biomedical Research Institute A Coruña (INIBIC)
Germán Bou: University Hospital A Coruña (CHUAC)–Biomedical Research Institute A Coruña (INIBIC)

Nature Communications, 2017, vol. 8, issue 1, 1-17

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.

Date: 2017
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DOI: 10.1038/ncomms15480

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