Syracuse

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

Archive ouverte

Lambert, Clara | Bachmann, Caroline | Gaillard, Marine | Hautcoeur, Antoine | Gloux, Karine | Guilbert, Thomas | Méhats, Celine | Prost, Bastien | Solgadi, Audrey | Abreu, Sonia | Andrieu, Muriel | Poyart, Claire | Gruss, Alexandra | Fouet, Agnes

Edité par CCSD -

Abstract In Streptococcus pyogenes , the fatty acid (FA) synthesis pathway FASII is feedback-controlled by the FabT repressor bound to an acyl-Acyl carrier protein. FabT defects are associated with attenuated virulence in animal models. Nevertheless, fabT point mutations arise in vivo . To resolve this paradox, we identified conditions and biotopes in which fabT behavior is defective, as being human tissues, cells, or cell filtrates. We then defined biotopes in which fabT mutants have a growth advantage, as being lipid rich. In a proof of concept we demonstrate that fabT mutants emerge in this context, due to FASII derepression, which prevents environmental FA incorporation. Energy dissipation is identified as the principal defect of fabT mutants, such that specific nutrients are consumed but do not promote growth. Our findings elucidate the nature of the link between FabT and virulence, provide a rationale for fabT mutant emergence, and identify the defect that causes attenuated fabT infection.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion