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:
http://www-ssrl.slac.stanford.edu/
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
