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An unnatural amino acid dependent, conditional Pseudomonas vaccine prevents bacterial infection

Author

Listed:
  • Michael Pigula

    (Scripps Research)

  • Yen-Chung Lai

    (Scripps Research
    University of California, San Diego)

  • Minseob Koh

    (Pusan National University)

  • Christian S. Diercks

    (Scripps Research)

  • Thomas F. Rogers

    (Scripps Research
    University of California, San Diego)

  • David A. Dik

    (Scripps Research)

  • Peter G. Schultz

    (Scripps Research)

Abstract

Live vaccines are ideal for inducing immunity but suffer from the need to attenuate their pathogenicity or replication to preclude the possibility of escape. Unnatural amino acids (UAAs) provide a strategy to engineer stringent auxotrophies, yielding conditionally replication incompetent live bacteria with excellent safety profiles. Here, we engineer Pseudomonas aeruginosa to maintain auxotrophy for the UAA p-benzoyl-l-phenylalanine (BzF) through its incorporation into the essential protein DnaN. In vivo evolution using an Escherichia coli-based two-hybrid selection system enabled engineering of a mutant DnaN homodimeric interface completely dependent on a BzF-specific interaction. This engineered strain, Pa Vaccine, exhibits undetectable escape frequency (

Suggested Citation

  • Michael Pigula & Yen-Chung Lai & Minseob Koh & Christian S. Diercks & Thomas F. Rogers & David A. Dik & Peter G. Schultz, 2024. "An unnatural amino acid dependent, conditional Pseudomonas vaccine prevents bacterial infection," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50843-7
    DOI: 10.1038/s41467-024-50843-7
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    References listed on IDEAS

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    1. Alexis J. Rovner & Adrian D. Haimovich & Spencer R. Katz & Zhe Li & Michael W. Grome & Brandon M. Gassaway & Miriam Amiram & Jaymin R. Patel & Ryan R. Gallagher & Jesse Rinehart & Farren J. Isaacs, 2015. "Correction: Corrigendum: Recoded organisms engineered to depend on synthetic amino acids," Nature, Nature, vol. 527(7577), pages 264-264, November.
    2. 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.
    3. Alexis J. Rovner & Adrian D. Haimovich & Spencer R. Katz & Zhe Li & Michael W. Grome & Brandon M. Gassaway & Miriam Amiram & Jaymin R. Patel & Ryan R. Gallagher & Jesse Rinehart & Farren J. Isaacs, 2015. "Recoded organisms engineered to depend on synthetic amino acids," Nature, Nature, vol. 518(7537), pages 89-93, February.
    4. Holly Hartman & Yuge Wang & Harry W Schroeder Jr & Xiangqin Cui, 2018. "Absorbance summation: A novel approach for analyzing high-throughput ELISA data in the absence of a standard," PLOS ONE, Public Library of Science, vol. 13(6), pages 1-12, June.
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