For COVID-19 vaccine updates, please review our information guide. For patient eligibility and scheduling availability, please visit VaccineTogetherNY.org.

Two enzymes with redundant fructose bisphosphatase activity sustain gluconeogenesis and virulence in Mycobacterium tuberculosis.

TitleTwo enzymes with redundant fructose bisphosphatase activity sustain gluconeogenesis and virulence in Mycobacterium tuberculosis.
Publication TypeJournal Article
Year of Publication2015
AuthorsGanapathy U, Marrero J, Calhoun S, Eoh H, de Carvalho LPedro Sori, Rhee K, Ehrt S
JournalNat Commun
Volume6
Pagination7912
Date Published2015 Aug 10
ISSN2041-1723
KeywordsFructose-Bisphosphatase, Gluconeogenesis, Lithium, Mycobacterium tuberculosis, Virulence
Abstract

The human pathogen Mycobacterium tuberculosis (Mtb) likely utilizes host fatty acids as a carbon source during infection. Gluconeogenesis is essential for the conversion of fatty acids into biomass. A rate-limiting step in gluconeogenesis is the conversion of fructose 1,6-bisphosphate to fructose 6-phosphate by a fructose bisphosphatase (FBPase). The Mtb genome contains only one annotated FBPase gene, glpX. Here we show that, unexpectedly, an Mtb mutant lacking GLPX grows on gluconeogenic carbon sources and has detectable FBPase activity. We demonstrate that the Mtb genome encodes an alternative FBPase (GPM2, Rv3214) that can maintain gluconeogenesis in the absence of GLPX. Consequently, deletion of both GLPX and GPM2 is required for disruption of gluconeogenesis and attenuation of Mtb in a mouse model of infection. Our work affirms a role for gluconeogenesis in Mtb virulence and reveals previously unidentified metabolic redundancy at the FBPase-catalysed reaction step of the pathway.

DOI10.1038/ncomms8912
Alternate JournalNat Commun
PubMed ID26258286
PubMed Central IDPMC4535450
Grant ListMC_UP_A253_1111 / / Medical Research Council / United Kingdom
R01 AI063446 / AI / NIAID NIH HHS / United States
U19 AI107774 / AI / NIAID NIH HHS / United States
MC_UP_1202/11 / / Medical Research Council / United Kingdom

Weill Cornell Medicine Microbiology and Immunology 1300 York Avenue, Box 62 New York, NY 10065 Phone: (212) 746-6505 Fax: (212) 746-8587