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Mucosal sugars delineate pyrazine vs pyrazinone autoinducer signaling in Klebsiella oxytoca

Author

Listed:
  • Randy Hamchand

    (Yale University
    Yale University)

  • Kevin Wang

    (Yale University)

  • Deguang Song

    (Yale University School of Medicine)

  • Noah W. Palm

    (Yale University School of Medicine)

  • Jason M. Crawford

    (Yale University
    Yale University
    Yale University School of Medicine)

Abstract

Virulent Klebsiella oxytoca strains are associated with gut and lung pathologies, yet our understanding of the molecular signals governing pathogenesis remains limited. Here, we characterized a family of K. oxytoca pyrazine and pyrazinone autoinducers and explored their roles in microbial and host signaling. We identified the human mucin capping sugar Neu5Ac as a selective elicitor of leupeptin, a protease inhibitor prevalent in clinical lung isolates of K. oxytoca, and leupeptin-derived pyrazinone biosynthesis. Additionally, we uncovered a separate pyrazine pathway, regulated by general carbohydrate metabolism, derived from a broadly conserved PLP-dependent enzyme. While both pyrazine and pyrazinone signaling induce iron acquisition responses, including enterobactin biosynthesis, pyrazinone signaling enhances yersiniabactin virulence factor production and selectively activates the proinflammatory human histamine receptor H4 (HRH4). Our findings suggest that the availability of specific carbohydrates delineates distinct autoinducer pathways in K. oxytoca that may have differential effects on bacterial virulence and host immune responses.

Suggested Citation

  • Randy Hamchand & Kevin Wang & Deguang Song & Noah W. Palm & Jason M. Crawford, 2024. "Mucosal sugars delineate pyrazine vs pyrazinone autoinducer signaling in Klebsiella oxytoca," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53185-6
    DOI: 10.1038/s41467-024-53185-6
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    References listed on IDEAS

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    1. Xin Chen & Stephan Schauder & Noelle Potier & Alain Van Dorsselaer & István Pelczer & Bonnie L. Bassler & Frederick M. Hughson, 2002. "Structural identification of a bacterial quorum-sensing signal containing boron," Nature, Nature, vol. 415(6871), pages 545-549, January.
    2. Katharine M. Ng & Jessica A. Ferreyra & Steven K. Higginbottom & Jonathan B. Lynch & Purna C. Kashyap & Smita Gopinath & Natasha Naidu & Biswa Choudhury & Bart C. Weimer & Denise M. Monack & Justin L., 2013. "Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens," Nature, Nature, vol. 502(7469), pages 96-99, October.
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