VIB: researchers uncover potent new target for antibiotic development

05 Aug 2009 | News

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Researchers at the Flanders Institute for Biotechnology (VIB) and the Department of Molecular and Cellular Interactions at the Vrije Universiteit Brussel (VUB) have uncovered the precise structure and function behind the toxin-antitoxin (T-A) system, by which bacteria protect their essential genes.

T-A genes are positioned near the genes they are protecting and contain instructions for both a toxin and its antitoxin. As long as the cell is producing both, all is well. However, if the sequence of DNA where the T-A gene is located is damaged or deleted, the production of toxin and antitoxin comes to a halt. Because the toxin is more stable than the antitoxin, it is broken down more slowly. Once the antitoxin is all gone, there is still enough toxin left to kill the bacterium.

Bacteria that lose their T-A gene, and are likely to have sustained damage to the important genes next to it, can no longer reproduce. Escherichia coli have such a T-A system in five different locations in their DNA, while Mycobacterium tuberculosis bacteria have them in 60 locations.

While the T-A mechanism has been known for a while, it was not clearly understood how the T-A gene operated. The VIB researchers have clarified in detail both the generation of the toxin and antitoxin, the mechanism of their interaction, and their different isoforms.

This opens the way for high throughput screening for compounds that imitate the toxin protein, block the antitoxin protein, or disrupt the interaction between the toxin and antitoxin.

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