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

Héloise Rytter1,2, Anne Jamet1,2, Jason Ziveri1,2

  • 1Université de Paris, Paris, France.

Plos Pathogens
|August 2, 2021
PubMed

Insights

The pentose phosphate pathway (PPP) is crucial for Francisella novicida virulence. Disrupting PPP genes impairs bacterial growth within host cells, highlighting its role in pathogenesis.

Area of Science:

  • Bacteriology
  • Microbial Pathogenesis
  • Metabolic Engineering

Background:

  • Metabolic pathways are critical for bacterial virulence and represent potential antibacterial targets.
  • The intracellular lifestyle of pathogenic bacteria necessitates specific metabolic adaptations.

Purpose of the Study:

  • To investigate the role of the pentose phosphate pathway (PPP) in the pathophysiology of Francisella novicida.
  • To elucidate the connections between the PPP and other metabolic networks within Francisella.

Main Methods:

  • Construction and analysis of PPP-inactivating mutants (tktA, rpiA, rpe).
  • Intramacrophage multiplication assays.
  • Time-lapse video microscopy.
  • Proteo-metabolomic analysis of mutant strains.

Main Results:

  • PPP inactivation mutants (tktA, rpiA, rpe) showed impaired intramacrophage multiplication within the first 24 hours.
  • rpiA and rpe mutants demonstrated a delayed ability to resume intracellular multiplication.
  • Proteo-metabolomic data revealed the PPP as a central metabolic hub connecting to glycolysis, TCA cycle, fatty acid degradation, and sulfur metabolism.

Conclusions:

  • The pentose phosphate pathway is essential for Francisella novicida's intracellular growth and pathogenesis.
  • The PPP acts as a key metabolic hub, integrating various pathways vital for bacterial survival in the host niche.

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