TUBERCULOSIS: New anti-TB drugs could target host proteins

Indian scientists have shown that new anti-tuberculosis drugs can be developed by targeting human cell proteins that the tuberculosis (TB) bacterium depends on for its survival during infection.
The findings by a research team led by Kanury Rao, head of immunology at the International Centre for Genetic Engineering and Biotechnology, New Delhi, were reported last month (15 April) in PLoS Pathogens.
TB, caused by the bacterium Mycobacterium tuberculosis, is a global public health threat that accounted for 9.4 million new cases and 1.8 million deaths worldwide in 2008, according to the WHO.
Poor compliance with treatment schedules, lasting six to nine months, using three standard anti-TB drugs has led to increasing drug resistance that calls for more expensive second-line drugs.
Globally there are about half a million new cases of multi-drug resistant TB (MDR-TB), half of them in China and India. An emerging worry is extremely drug-resistant TB (XDR –TB) in which patients no longer respond to even second-line drugs.
An ideal new anti-TB drug would treat both MDR-TB and XDR-TB, as well as 'latent' cases where symptoms are not evident, Rao told SciDev.Net. It should also significantly reduce the duration of treatment to combat increasing drug resistance, he said.
Rao said the human cell or 'host' factors are important for survival of drug resistant strains of the TB bacterium
The team had earlier identified all the 275 human host cell proteins being used by M. tuberculosis. Of these, 74 were critical for the bacterium's survival, it reported in March in the journal Cell.
The next step is to identify chemicals that inhibit the critical proteins in human cells and develop them as drugs for TB. Rao's strategy is to simultaneously target the proteins with multiple inhibitors and to quickly eliminate the TB bacterium with minimum damage to the host cell.
Eventually the aim is to use chemicals whose inhibitory effect can be reversed after the elimination of the TB bacterium, thereby allowing the human cells to get back to normal functioning.
The new research is significant as it looks at an aspect of TB that has not been studied before, observes Zakir Thomas, project director of the Open Source Drug Discovery Foundation, an initiative launched by India's Council of Scientific and Industrial Research.
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