The pentose phosphate pathway constitutes a major metabolic hub in pathogenic Francisella

PLoS Pathog. 2021 Aug 2;17(8):e1009326. doi: 10.1371/journal.ppat.1009326. eCollection 2021 Aug.


Metabolic pathways are now considered as intrinsic virulence attributes of pathogenic bacteria and thus represent potential targets for antibacterial strategies. Here we focused on the role of the pentose phosphate pathway (PPP) and its connections with other metabolic pathways in the pathophysiology of Francisella novicida. The involvement of the PPP in the intracellular life cycle of Francisella was first demonstrated by studying PPP inactivating mutants. Indeed, we observed that inactivation of the tktA, rpiA or rpe genes severely impaired intramacrophage multiplication during the first 24 hours. However, time-lapse video microscopy demonstrated that rpiA and rpe mutants were able to resume late intracellular multiplication. To better understand the links between PPP and other metabolic networks in the bacterium, we also performed an extensive proteo-metabolomic analysis of these mutants. We show that the PPP constitutes a major bacterial metabolic hub with multiple connections to glycolysis, the tricarboxylic acid cycle and other pathways, such as fatty acid degradation and sulfur metabolism. Altogether our study highlights how PPP plays a key role in the pathogenesis and growth of Francisella in its intracellular niche.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism*
  • Drosophila melanogaster / microbiology
  • Francisella / metabolism
  • Francisella / pathogenicity*
  • Gene Expression Regulation, Bacterial
  • Glycolysis
  • Gram-Negative Bacterial Infections / microbiology*
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Male
  • Metabolome*
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • Pentose Phosphate Pathway*
  • Proteome*


  • Bacterial Proteins
  • Proteome

Grant support

These studies were supported by INSERM, CNRS and Université de Paris. Jason Ziveri and Héloise Rytter were supported by a fellowship from the “Délégation Générale à l’Armement”. Elodie Ramond was supported by the Agence Nationale de la Recherche (ANR-15-CE15-0017 StopBugEntry). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.