Free Glucosylglycerate
Is a Novel Marker of Nitrogen Stress in <i>Mycobacterium smegmatis</i>
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Abstract
Nitrogen is an essential element for bacterial growth,
and as such, bacteria have evolved several pathways to assimilate
nitrogen and adapt to situations of nitrogen limitation. However,
the adaptation of mycobacteria to nitrogen stress and the regulation
of the stress response pathways is unknown. Identification of key
metabolites produced by mycobacteria during nitrogen stress could
therefore provide important insights into mycobacterial survival strategies.
Here we used NMR-based metabolomics to monitor and quantify intracellular
and extracellular metabolite levels (metabolic footprinting) in <i>Mycobacterium smegmatis</i> grown under nitrogen-limiting and
nitrogen-rich conditions. There were several metabolic differences
between the two conditions: following nitrogen run-out, there was
an increase in intracellular α-ketoglutarate and a decrease
in intracellular glutamine and glutamate levels. In addition, a sugar-derived
compound accumulated in nitrogen-starved cells that was subsequently
assigned as glucosylglycerate (GGA). Free GGA production was responsive
to nitrogen stress in <i>M. smegmatis</i> but not to oxidative
or osmotic stress; lack of a functional GGA synthesis pathway slightly
reduced growth and decreased ammonium uptake rates under nitrogen-limiting
conditions. Hence, GGA could contribute to the fitness of mycobacteria
under nitrogen limitation