Deletion of transketolase triggers a stringent metabolic response in promastigotes and loss of virulence in amastigotes of Leishmania mexicana - Centre de Résonance Magnétique des Systèmes Biologiques Accéder directement au contenu
Article Dans Une Revue PLoS Pathogens Année : 2018

Deletion of transketolase triggers a stringent metabolic response in promastigotes and loss of virulence in amastigotes of Leishmania mexicana

Résumé

Transketolase (TKT) is part of the non-oxidative branch of the pentose phosphate pathway (PPP). Here we describe the impact of removing this enzyme from the pathogenic protozoan Leishmania mexicana. Whereas the deletion had no obvious effect on cultured promastigote forms of the parasite, the Δtkt cells were not virulent in mice. Δtkt promastigotes were more susceptible to oxidative stress and various leishmanicidal drugs than wild-type, and metabolomics analysis revealed profound changes to metabolism in these cells. In addition to changes consistent with those directly related to the role of TKT in the PPP, central carbon metabolism was substantially decreased, the cells consumed significantly less glucose, flux through glycolysis diminished, and production of the main end products of metabolism was decreased. Only minor changes in RNA abundance from genes encoding enzymes in central carbon metabolism, however, were detected although fructose-1,6-bisphosphate aldolase activity was decreased twofold in the knockout cell line. We also showed that the dual localisation of TKT between cytosol and glycosomes is determined by the C-terminus of the enzyme and by engineering different variants of the enzyme we could alter its sub-cellular localisation. However, no effect on the overall flux of glucose was noted irrespective of whether the enzyme was found uniquely in either compartment, or in both.

Domaines

Parasitologie
Fichier principal
Vignette du fichier
journal.ppat.1006953.pdf (9.45 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

hal-02421191 , version 1 (20-12-2019)

Identifiants

Citer

Julie Kovářová, Andrew Pountain, David Wildridge, Stefan Weidt, Frédéric Bringaud, et al.. Deletion of transketolase triggers a stringent metabolic response in promastigotes and loss of virulence in amastigotes of Leishmania mexicana. PLoS Pathogens, 2018, 14 (3), pp.e1006953. ⟨10.1371/journal.ppat.1006953⟩. ⟨hal-02421191⟩

Collections

CNRS CRMSB
61 Consultations
55 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More