title: Possible links between stress defense and the tricarboxylic acid (TCA) cycle in Francisella pathogenesis.
abstract: Francisella tularensis is a highly infectious bacterium causing the zoonotic disease tularemia. In vivo, this facultative intracellular bacterium survives and replicates mainly in the cytoplasm of infected cells. We have recently identified a genetic locus, designated moxR that is important for stress resistance and intramacrophage survival of F. tularensis. In the present work, we used tandem affinity purification coupled to mass spectrometry to identify in vivo interacting partners of three proteins encoded by this locus: the MoxR-like ATPase (FTL_0200), and two proteins containing motifs predicted to be involved in protein-protein interactions, bearing von Willebrand A (FTL_0201) and tetratricopeptide (FTL_0205) motifs. The three proteins were designated here for simplification, MoxR, VWA1, and TPR1, respectively. MoxR interacted with 31 proteins, including various enzymes. VWA1 interacted with fewer proteins, but these included the E2 component of 2-oxoglutarate dehydrogenase and TPR1. The protein TPR1 interacted with one hundred proteins, including the E1 and E2 subunits of both oxoglutarate and pyruvate dehydrogenase enzyme complexes, and their common E3 subunit. Remarkably, chromosomal deletion of either moxR or tpr1 impaired pyruvate dehydrogenase and oxoglutarate dehydrogenase activities, supporting the hypothesis of a functional role for the interaction of MoxR and TPR1 with these complexes. Altogether, this work highlights possible links between stress resistance and metabolism in F. tularensis virulence.
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Bâtiment Leriche. 96 rue Didot 75993 Paris Cedex 14 - France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Dieppedale
authors.forename: Gael
authors.initials: G
authors.lastname: Gesbert
authors.forename: Elodie
authors.initials: E
authors.lastname: Ramond
authors.forename: Cerina
authors.initials: C
authors.lastname: Chhuon
authors.forename: Iharilalao
authors.initials: I
authors.lastname: Dubail
authors.forename: Marion
authors.initials: M
authors.lastname: Dupuis
authors.forename: Ida Chiara
authors.initials: IC
authors.lastname: Guerrera
authors.forename: Alain
authors.initials: A
authors.lastname: Charbit
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D002952:Citric Acid Cycle / Q000502:physiology*; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D005604:Francisella tularensis / Q000378:metabolism* / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D013312:Stress, Physiological; D014406:Tularemia
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial