The metabolic enzyme fructose-1,6-bisphosphate aldolase acts as a transcriptional regulator in pathogenic Francisella

  • Nat Commun. 2017 Oct 11;8(1):853. doi: 10.1038/s41467-017-00889-7.
Jason Ziveri  1  2 ,  Fabiola Tros  1  2 ,  Ida Chiara Guerrera  1  3 ,  Cerina Chhuon  1  3 ,  Mathilde Audry  1  2 ,  Marion Dupuis  1  2 ,  Monique Barel  1  2 ,  Sarantis Korniotis  1  4 ,  Simon Fillatreau  1  4 ,  Lara Gales  5 ,  Edern Cahoreau  5 ,  Alain Charbit  6  7
Affiliations
  • 1. Université Paris Descartes, Sorbonne Paris Cité, Bâtiment Leriche, Paris, 75993, France.
  • 2. INSERM U1151 - CNRS UMR 8253, Institut Necker-Enfants Malades, Team 11: Pathogenesis of Systemic Infections, Paris, 75993, France.
  • 3. Plateforme Protéomique 3P5-Necker, Structure Fédérative de Recherche Necker and Université Paris Descartes, INSERM US24/CNRS UMS3633, Paris, 75993, France.
  • 4. INSERM U1151 - CNRS UMR 8253, Institut Necker-Enfants Malades, Team 16: Immunity in Health and Disease, Paris, 75993, France.
  • 5. Metatoul Platform, LISBP, Université de Toulouse, CNRS, INRA, INSA, Toulouse, 31077, France.
  • 6. Université Paris Descartes, Sorbonne Paris Cité, Bâtiment Leriche, Paris, 75993, France. [email protected].
  • 7. INSERM U1151 - CNRS UMR 8253, Institut Necker-Enfants Malades, Team 11: Pathogenesis of Systemic Infections, Paris, 75993, France. [email protected].
PMID: 29021545 DOI: 10.1038/s41467-017-00889-7
Abstract

The enzyme fructose-bisphosphate aldolase occupies a central position in glycolysis and gluconeogenesis pathways. Beyond its housekeeping role in metabolism, fructose-bisphosphate aldolase has been involved in additional functions and is considered as a potential target for drug development against pathogenic bacteria. Here, we address the role of fructose-bisphosphate aldolase in the Bacterial pathogen Francisella novicida. We demonstrate that fructose-bisphosphate aldolase is important for Bacterial multiplication in macrophages in the presence of gluconeogenic substrates. In addition, we unravel a direct role of this metabolic enzyme in transcription regulation of genes katG and rpoA, encoding catalase and an RNA polymerase subunit, respectively. We propose a model in which fructose-bisphosphate aldolase participates in the control of host redox homeostasis and the inflammatory immune response.The enzyme fructose-bisphosphate aldolase (FBA) plays central roles in glycolysis and gluconeogenesis. Here, Ziveri et al. show that FBA of the pathogen Francisella novicida acts, in addition, as a transcriptional regulator and is important for Bacterial multiplication in macrophages.