The double-edged role of FASII regulator FabT in Streptococcus pyogenes infection.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
04 Oct 2024
04 Oct 2024
Historique:
received:
14
02
2024
accepted:
16
09
2024
medline:
5
10
2024
pubmed:
5
10
2024
entrez:
4
10
2024
Statut:
epublish
Résumé
In Streptococcus pyogenes, the type II fatty acid (FA) synthesis pathway FASII is feedback-controlled by the FabT repressor bound to an acyl-Acyl carrier protein. Although FabT defects confer reduced virulence in animal models, spontaneous fabT mutants arise in vivo. We resolved this paradox by characterizing the conditions and mechanisms requiring FabT activity, and those promoting fabT mutant emergence. The fabT defect leads to energy dissipation, limiting mutant growth on human tissue products, which explains the FabT requirement during infection. Conversely, emerging fabT mutants show superior growth in biotopes rich in saturated FAs, where continued FASII activity limits their incorporation. We propose that membrane alterations and continued FASII synthesis are the primary causes for increased fabT mutant mortality in nutrient-limited biotopes, by failing to stop metabolic consumption. Our findings elucidate the rationale for emerging fabT mutants that improve bacterial survival in lipid-rich biotopes, but lead to a genetic impasse for infection.
Identifiants
pubmed: 39366941
doi: 10.1038/s41467-024-52637-3
pii: 10.1038/s41467-024-52637-3
doi:
Substances chimiques
Bacterial Proteins
0
Fatty Acids
0
Repressor Proteins
0
Fatty Acid Synthase, Type II
EC 6.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8593Subventions
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-16-CE15-0013
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-22-AAMR-0007
Organisme : Fondation pour la Recherche Médicale (Foundation for Medical Research in France)
ID : DBF20161136769
Organisme : Fondation pour la Recherche Médicale (Foundation for Medical Research in France)
ID : FDT202106012831
Informations de copyright
© 2024. The Author(s).
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