Mucosal sugars delineate pyrazine vs pyrazinone autoinducer signaling in Klebsiella oxytoca.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 Oct 2024
16 Oct 2024
Historique:
received:
15
03
2024
accepted:
03
10
2024
medline:
16
10
2024
pubmed:
16
10
2024
entrez:
15
10
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39406708
doi: 10.1038/s41467-024-53185-6
pii: 10.1038/s41467-024-53185-6
doi:
Substances chimiques
Pyrazines
0
Virulence Factors
0
yersiniabactin
0
Bacterial Proteins
0
Phenols
0
Thiazoles
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8902Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : 1RM1GM141649-01
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : T32GM067543
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : 1RM1GM141649-01
Organisme : U.S. Department of Health & Human Services | NIH | NIH Office of the Director (OD)
ID : 1S10OD030363-01A1
Informations de copyright
© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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