Skip to main content

Research Repository

Advanced Search

Metabolic fluxes for nutritional flexibility of Mycobacterium tuberculosis.

Metabolic fluxes for nutritional flexibility of Mycobacterium tuberculosis. Thumbnail


The co-catabolism of multiple host-derived carbon substrates is required by Mycobacterium tuberculosis (Mtb) to successfully sustain a tuberculosis infection. However, the metabolic plasticity of this pathogen and the complexity of the metabolic networks present a major obstacle in identifying those nodes most amenable to therapeutic interventions. It is therefore critical that we define the metabolic phenotypes of Mtb in different conditions. We applied metabolic flux analysis using stable isotopes and lipid fingerprinting to investigate the metabolic network of Mtb growing slowly in our steady-state chemostat system. We demonstrate that Mtb efficiently co-metabolises either cholesterol or glycerol, in combination with two-carbon generating substrates without any compartmentalisation of metabolism. We discovered that partitioning of flux between the TCA cycle and the glyoxylate shunt combined with a reversible methyl citrate cycle is the critical metabolic nodes which underlie the nutritional flexibility of Mtb. These findings provide novel insights into the metabolic architecture that affords adaptability of bacteria to divergent carbon substrates and expand our fundamental knowledge about the methyl citrate cycle and the glyoxylate shunt.

Acceptance Date Mar 31, 2021
Publication Date May 1, 2021
Journal Molecular Systems Biology
Publisher Wiley
Pages e10280 - ?
Keywords chemostat; metabolic flux; metabolism; Mycobacterium tuberculosis; tuberculosis
Publisher URL


Downloadable Citations