Glucose phosphorylation is required for Mycobacterium tuberculosis persistence in mice.

TitleGlucose phosphorylation is required for Mycobacterium tuberculosis persistence in mice.
Publication TypeJournal Article
Year of Publication2013
AuthorsMarrero J, Trujillo C, Rhee KY, Ehrt S
JournalPLoS Pathog
Date Published2013 Jan
KeywordsAnimals, Bacterial Proteins, Carbon Radioisotopes, Disease Models, Animal, Female, Gene Knockout Techniques, Glucokinase, Glucose, Host-Pathogen Interactions, Metabolomics, Mice, Mice, Inbred C57BL, Mice, Knockout, Mutation, Mycobacterium tuberculosis, Phosphorylation, Phosphotransferases, Substrate Specificity, Tuberculosis

Mycobacterium tuberculosis (Mtb) is thought to preferentially rely on fatty acid metabolism to both establish and maintain chronic infections. Its metabolic network, however, allows efficient co-catabolism of multiple carbon substrates. To gain insight into the importance of carbohydrate substrates for Mtb pathogenesis we evaluated the role of glucose phosphorylation, the first reaction in glycolysis. We discovered that Mtb expresses two functional glucokinases. Mtb required the polyphosphate glucokinase PPGK for normal growth on glucose, while its second glucokinase GLKA was dispensable. (13)C-based metabolomic profiling revealed that both enzymes are capable of incorporating glucose into Mtb's central carbon metabolism, with PPGK serving as dominant glucokinase in wild type (wt) Mtb. When both glucokinase genes, ppgK and glkA, were deleted from its genome, Mtb was unable to use external glucose as substrate for growth or metabolism. Characterization of the glucokinase mutants in mouse infections demonstrated that glucose phosphorylation is dispensable for establishing infection in mice. Surprisingly, however, the glucokinase double mutant failed to persist normally in lungs, which suggests that Mtb has access to glucose in vivo and relies on glucose phosphorylation to survive during chronic mouse infections.

Alternate JournalPLoS Pathog
PubMed ID23326232
PubMed Central IDPMC3542180
Grant ListR01 AI063446 / AI / NIAID NIH HHS / United States
AI063446 / AI / NIAID NIH HHS / United States
AI081094 / AI / NIAID NIH HHS / United States

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