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Scientific Highlight
D.P. Giedroc Research
G.N. George Research
Press Release

31 January 2007

  On the Role of Copper Regulation in a M. tuberculosis Repressor

summary written by Brad Plummer, SLAC Communication Office


Scientists have discovered a gene for a protein that regulates the cellular response to copper in the bacterium that causes tuberculosis. These findings, reported in the January issue of Nature Chemical Biology, explain how a wide variety of bacteria control copper concentrations within their cells, and this understanding could lead to new treatments for tuberculosis.

The team discovered the gene that encodes a "Copper-sensitive operon Repressor" (CsoR), which controls the production of copper-binding proteins and is present in many types of bacteria. X-ray absorption spectroscopy (XAS), measured mainly on SSRL's beam line 9-3, on purified samples of the copper-binding protein from M. tuberculosis was used to discern the chemical mechanism behind the copper-binding protein.

Previous work had shown that CsoR was part of a cluster of genes active in M. tuberculosis infecting the lungs of mice. Analysis of the DNA sequence of a nearby gene led researchers to hypothesize that it encoded a protein that acts as a "copper pump" that drives excess copper out of the cell, and that CsoR was the critical regulator of this process.

Copper is a biologically essential element. Its levels within a cell must be carefully controlled because too much can cause cell death, but the cell needs copper ions to break down reactive compounds that would otherwise destroy important proteins, DNA, and lipids within the cell. Copper ions are prevented from damaging the cell by regulatory proteins that sense the metal and turn on the production of other proteins that help mitigate its deadly effects. However, the gene responsible for turning on these proteins and the mechanism behind how the protein works had not been previously identified in many bacteria.

To learn more about this research see the full scientific highlight at: research/highlights_archive/CsoR.html

Liu, T., Ramesh, A., Ma, Z., Ward, S. K., Zhang, L., George, G. N., Talaat, A. M., Sacchettini, G. C., Giedroc, D. P. "CsoR is a novel Mycobacterium tuberculosis copper-sensing transcriptional regulator". Nature Chem. Bio., 2007, 3, 60-68