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

Author

Listed:
  • 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))

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.

Suggested Citation

  • Maria P. Cabral & Patricia García & Alejandro Beceiro & Carlos Rumbo & Astrid Pérez & Miriam Moscoso & Germán Bou, 2017. "Design of live attenuated bacterial vaccines based on D-glutamate auxotrophy," Nature Communications, Nature, vol. 8(1), pages 1-17, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15480
    DOI: 10.1038/ncomms15480
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