New antibacterial targets?

Small molecules that bind to segments of RNA called riboswitches could represent a novel class of antibiotics according to a report in the January issue of Nature Chemical Biology.

Small segments of RNA called riboswitches can control gene expression in response to the presence of bacterial metabolic products. The lysine riboswitch controls the biosynthesis of lysine, an essential amino acid for bacteria. Ronald Breaker and colleagues created small molecules that are chemically similar to lysine. They found that some of these lysine 'analogs' bind to the lysine riboswitch and as a result prevent lysine biosynthesis thereby stopping bacterial growth. The authors suggest that rationally targeting riboswitches -- which are involved in sensing many critical bacterial metabolites - could provide a new class of antibiotics.

Mycobacterium tuberculosis copper regulator found

Scientists have discovered a protein that controls gene expression in response to copper in the bacterium that causes most cases of tuberculosis and potentially a wide variety of other bacteria. These findings, reported in the January issue of Nature Chemical Biology, explain how many bacteria control copper concentrations within cells and this understanding could help in the design of new treatments for tuberculosis.

Copper is an essential element, but the levels within a cell must be carefully controlled as too much can cause cell death. Copper ions are prevented from damaging the cell by regulatory proteins that trap the metal. However, a mechanism for controlling the expression of these proteins had not previously been identified in many bacteria. Giedroc and colleagues have discovered a protein -- CsoR -- that regulates the expression of the copper-binding proteins and is present in many types of bacteria.

The discovery of a common copper-sensitive repressor helps scientists to understand how bacteria control concentrations of metals, and may provide a novel target for designing antibiotics to treat diseases including tuberculosis.

Antibacterial lysine analogs that target lysine riboswitches

Kenneth F Blount, Joy Xin Wang, Jinsoo Lim, Narasimhan Sudarsan and Ronald R Breaker

Published online: 03 December 2006 | doi 10.1038/nchembio842

Abstract | Full text | PDF | Supplementary information

CsoR is a novel Mycobacterium tuberculosis copper-sensing transcriptional regulator

Tong Liu, Arati Ramesh, Zhen Ma, Sarah K Ward, Limei Zhang, Graham N George, Adel M Talaat, James C Sacchettini and David P Giedroc

Published online: 03 December 2006 | doi 10.1038/nchembio844

Abstract | Full text | PDF | Supplementary information