Possible inhibitors against X-DR TB discovered

Researchers based at South Africa's CSIR have made a breakthrough in isolating five compounds that show efficacy against X-DR TB, the virulent strain of tuberculosis that has gripped the world. X-DR (extensively drug-resistant tuberculosis, those strains of TB resistant to both first and second line drugs), leaves infected people virtually untreatable with currently available anti-TB drugs.

The World Health Organization states that X-DR TB has been identified in all regions of the world and is found most frequently in the countries of the former Soviet Union and in Asia. In South Africa, it was first reported late last year. More than 200 deaths have since been reported.

According to Dr Colin Kenyon, who leads the structural biology research group, the CSIR's investigation into inhibitors against these X-DR TB strains took place as a follow up to an Innovation Fund project aimed at developing inhibitors to Mycobacterium tuberculosis, the bacterium that causes most cases of TB. The structural biology group, based in Modderfontein, identifies, elucidates and validates potential new drug targets. This knowledge is then used for rational inhibitor design and lead molecule modification. The group primarily focuses on infectious diseases.

It was while working on the isolation of novel antibiotics by rational drug design using computational techniques, organic synthesis and molecular biology, that the group found several compounds inhibitory to M. tuberculosis.

"It was decided to determine if these same compounds are also inhibitory to X-DR TB," said Kenyon. The research was conducted in conjunction with Stellenbosch University in September. Initially about 200 compounds were tested, the selection of which was based on the results of a novel in vitro screening programme against a new anti-bacterial target discovered within the programme. None of the compounds that successfully passed the X-DR TB screening test was found to be cyto-toxic. "They were found to kill X-DR. What is of significance, is that the inhibition of M. tuberculosis by these compounds is not strain dependent," said Kenyon.

The European Union has committed itself to invest in the expansion of this project, while the CSIR group has also approached the Innovation Fund for financial assistance. - CSIR - E-News.

 

December 2007