Unknown

Dataset Information

0

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


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.

SUBMITTER: Ganapathy U 

PROVIDER: S-EPMC4535450 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Ganapathy Uday U   Marrero Joeli J   Calhoun Susannah S   Eoh Hyungjin H   de Carvalho Luiz Pedro Sorio LPS   Rhee Kyu K   Ehrt Sabine S  

Nature communications 20150810


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  ...[more]

Similar Datasets

| S-EPMC3107150 | biostudies-literature
| S-EPMC5485559 | biostudies-literature
| S-EPMC2323843 | biostudies-literature
| S-EPMC5892879 | biostudies-literature
| S-EPMC1459384 | biostudies-literature
| S-EPMC4162811 | biostudies-literature
| S-EPMC6400660 | biostudies-literature
| S-EPMC4550268 | biostudies-literature
| S-EPMC2862998 | biostudies-literature
2008-08-08 | GSE12382 | GEO