Partner: Sivaramesh Wigneshweraraj

Imperial College London (GB)

Recent publications
1.Schumacher J., Behrends V., Pan Z., Brown D.R., Heydenreich F., Lewis M.R., Bennett M.H., Razzaghi B., Komorowski M., Barahona M., Stumpf M.P.H., Wigneshweraraj S., Bundy J.G., Buck M., Nitrogen and carbon status are integrated at the transcriptional level by the nitrogen regulator NtrC in vivo, mBio, ISSN: 2150-7511, DOI: 10.1128/mBio.00881-13, Vol.4, pp.00881-1-13, 2013
Abstract:

Nitrogen regulation in Escherichia coli is a model system for gene regulation in bacteria. Growth on glutamine as a sole nitrogen source is assumed to be nitrogen limiting, inferred from slow growth and strong NtrB/NtrC-dependent gene activation. However, we show that under these conditions, the intracellular glutamine concentration is not limiting but 5.6-fold higher than in ammonium-replete conditions; in addition, α-ketoglutarate concentrations are elevated. We address this glutamine paradox from a systems perspective. We show that the dominant role of NtrC is to regulate glnA transcription and its own expression, indicating that the glutamine paradox is not due to NtrC-independent gene regulation. The absolute intracellular NtrC and GS concentrations reveal molecular control parameters, where NtrC-specific activities were highest in nitrogen-starved cells, while under glutamine growth, NtrC showed intermediate specific activity. We propose an in vivo model in which α-ketoglutarate can derepress nitrogen regulation despite nitrogen sufficiency.

Affiliations:
Schumacher J.-Imperial College London (GB)
Behrends V.-Imperial College London (GB)
Stumpf M.P.H.-Imperial College London (GB)
Wigneshweraraj S.-Imperial College London (GB)
Bundy J.G.-Imperial College London (GB)
Buck M.-Imperial College London (GB)
Pan Z.-Imperial College London (GB)
Brown D.R.-Imperial College London (GB)
Heydenreich F.-Imperial College London (GB)
Lewis M.R.-Imperial College London (GB)
Bennett M.H.-Imperial College London (GB)
Razzaghi B.-Imperial College London (GB)
Komorowski M.-IPPT PAN
Barahona M.-Imperial College London (GB)