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Cited by 8Bacterial Genetics and BiotechnologyStreptococcal Infections and TreatmentsCancer, Lipids, and Metabolism

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The double-edged role of FASII regulator FabT in Streptococcus pyogenes infection

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Lambert, Clara, Gaillard, Marine, Wongdontree, Paprapach, Bachmann, Caroline, Hautcoeur, Antoine, Gloux, Karine, Guilbert, Thomas, Méhats, Celine, Prost, Bastien, Solgadi, Audrey, Abreu, Sonia, Andrieu, Muriel, Poyart, Claire, Gruss, Alexandra, Fouet, Agnes·2024·Nature Communications
DOI 10.1038/s41467-024-52637-3PMC PMC11452403

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Abstract

Abstract 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. Despite FabT defects being linked to reduced virulence in animal models, spontaneous fabT mutants arise in vivo . To resolve this paradox, we characterized the conditions and mechanisms that require FabT activity, and those that promote fabT mutant emergence. The primary fabT mutant defect is energy dissipation: specific nutrients are consumed, but the mutant fails to grow on human tissue, cells, or cell filtrates where nutrients are limited. These features explain the FabT requirement during infection. Conversely, fabT mutants exhibited a marked growth advantage over the wild-type in biotopes rich in saturated FAs. fabT mutants emerge in this context, where continued FASII activity prevented environmental FA incorporation. An ex vivo muscle model demonstrated that wild-type S. pyogenes was inhibited, while fabT mutant growth was stimulated, but conditional to FASII activity. Our findings elucidate the rationale for emerging fabT mutants that improve survival in lipid-rich biotopes, but lead to a genetic impasse for infection.

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Metadata

Authors
Lambert, C., Gaillard, M., Wongdontree, P., Bachmann, C., Hautcoeur, A., Gloux, K., Guilbert, T., Méhats, C., Prost, B., Solgadi, A., Abreu, S., Andrieu, M., Poyart, C., Gruss, A., & Fouet, A.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • AgroParisTech (FR)
  • Université Paris-Saclay (FR)
Corresponding author
Gruss, Alexandra
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2024-10-04
Volume
15
Issue
1
Pages
8593-8593
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-024-52637-3
PMC
PMC11452403
OpenAlex
W4403135616
Cited by
8
References
3
Citations by year
2026: 5 · 2025: 1 · 2024: 1
FWCI
1.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Agence Nationale de la Recherche (ANR-22-AAMR-0007, ANR‐10_INBS‐04, ANR-10, ANR-16-CE15-0013)
  • Fondation pour la Recherche Médicale (DBF20161136769, FDT202106012831)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Health Sciences › Medicine › Infectious Diseases › Streptococcal Infections and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
Streptococcus pyogenes, fatty acid synthesis regulation, acyl-acyl carrier protein, bacterial virulence, saturated fatty acids, energy dissipation, bacterial fitness
MeSH terms
Animals, Bacterial Proteins, Fatty Acids, Female, Humans, Mutation, Repressor Proteins, Streptococcal Infections, Streptococcus pyogenes, Virulence, Gene Expression Regulation, Bacterial, Mice, Fatty Acid Synthase, Type II

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