Open AccessThe pentose phosphate pathway constitutes a major metabolic hub in pathogenic Francisella
Author(s) -
Héloïse Rytter,
Anne Jamet,
Jason Ziveri,
Elodie Ramond,
Mathieu Coureuil,
Pauline Lagouge-Roussey,
Daniel Euphrasie,
Fabiola Tros,
Nicolas Goudin,
Cérina Chhuon,
Ivan Nemazanyy,
Fabrício Edgar de Moraes,
Carlos Alberto Labate,
Ida Chiara Guerrera,
Alain Charbit
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009326
Subject(s) - francisella , pentose phosphate pathway , metabolic pathway , citric acid cycle , intracellular , biology , intracellular parasite , glycolysis , mutant , microbiology and biotechnology , francisella tularensis , metabolic network , biochemistry , virulence , metabolism , gene
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.