Nitrogen metabolism in Mycobacterium tuberculosis: a systems-based approach
Poster Apr 06, 2018
PiyaliS Basu, Dany JV Beste, KhushbooBorah, Kerstin J Williams, Johnjoe McFadden.
Several studies have already shown Mycobacterium tuberculosis (Mtb) obtains its carbon from host-derived nutrients and exploits specific metabolic pathways during infection.
In comparison to carbon, the processes Mtb uses to acquire and assimilate nitrogen (N) from the host is poorly studied despite N also being an essential component of biomolecules.
Our previous studies suggested the hypothesis that Mtb obtains N from a diverse range of intracellular nutrients including amino acids.
Here, we use a novel system’s based three-pronged approach to define pathways for uptake and assimilation of N. This consists of transposon mutagenesis, 15N isotopologueprofiling of intracellular Mtb, and performing flux analysis using 13C/15N isotopologue profiling in continuous culture.
Using this system’s strategy to study Mtb metabolism will help determine which N sources are required for ex vivo Mtb survival and the uptake and assimilation pathways involved to ultimately identify novel drug targets to treat TB.
Primary Human Hepatocyte (PHH) culture provides the closest in vitro model to human liver that can produce a metabolic profile of a given drug very similar to that found in vivo. Recently we have developed an easy-to-assemble user-friendly in vitro Primary Human Hepatocyte (PHH) 3D-spheroid modelREAD MORE