Design of live attenuated bacterial vaccines based on D-glutamate auxotrophy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28548079.
- Also identified by DOI 10.1038/ncomms15480 and PMC identifier 5458566.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Bacteria
- Bacterial Infections
- Bacterial Vaccines
- Glutamic Acid
- Vaccines, Attenuated