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
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

8593

Subventions

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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Auteurs

Clara Lambert (C)

Université Paris Cité, Institut Cochin, INSERM, U1016, CNRS, UMR8104, Paris, France.
Molecular Microbiology and Structural Biochemistry, CNRS, UMR5086, Université de Lyon, Lyon, France.

Marine Gaillard (M)

Université Paris Cité, Institut Cochin, INSERM, U1016, CNRS, UMR8104, Paris, France.

Paprapach Wongdontree (P)

Micalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, Jouy en Josas, France.

Caroline Bachmann (C)

Université Paris Cité, Institut Cochin, INSERM, U1016, CNRS, UMR8104, Paris, France.

Antoine Hautcoeur (A)

Université Paris Cité, Institut Cochin, INSERM, U1016, CNRS, UMR8104, Paris, France.

Karine Gloux (K)

Micalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, Jouy en Josas, France.

Thomas Guilbert (T)

Université Paris Cité, Institut Cochin, INSERM, U1016, CNRS, UMR8104, Paris, France.

Celine Méhats (C)

Université Paris Cité, Institut Cochin, INSERM, U1016, CNRS, UMR8104, Paris, France.

Bastien Prost (B)

UMS-IPSIT - Plateforme SAMM, Université Paris-Saclay, Orsay, France.

Audrey Solgadi (A)

UMS-IPSIT - Plateforme SAMM, Université Paris-Saclay, Orsay, France.

Sonia Abreu (S)

Lipides: Systèmes Analytiques et Biologiques, Université Paris-Saclay, Orsay, France.

Muriel Andrieu (M)

Université Paris Cité, Institut Cochin, INSERM, U1016, CNRS, UMR8104, Paris, France.

Claire Poyart (C)

Université Paris Cité, Institut Cochin, INSERM, U1016, CNRS, UMR8104, Paris, France.
AP-HP Centre-Université Paris Cité, Paris, France.

Alexandra Gruss (A)

Micalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, Jouy en Josas, France. alexandra.gruss@inrae.fr.

Agnes Fouet (A)

Université Paris Cité, Institut Cochin, INSERM, U1016, CNRS, UMR8104, Paris, France. agnes.fouet@inserm.fr.

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