Local scientists make major TB breakthrough

A team from the Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, has become the first in the world to discover the precise molecular mechanism which makes anti-tuberculosis (TB) drugs effective. The breakthrough will provide a fundamental structural basis for the development of new anti-TB drugs targeting resistance.

Their findings have been published in the international journal Science.

TB, caused by the bacteria Mycobacterium tuberculosis, is one to the most common fatal diseases worldwide. Popular anti-TB drugs in current clinical therapeutics have been developed over more than half a century. Of great concern, however, is the emergence of multi-drug-resistant and extensively drug-resistant TB strains. Consequently there is an urgent need to understand the drug targets and to develop new anti-TB drugs.

According to the researchers, Mycobacterium tuberculosis has a complex cell wall which acts as a natural barrier surrounding the cell membrane, so inhibition of the cell wall assembly is an established strategy for anti-TB chemotherapy. The first-line drug ethambutol is known to target a kind of proteins that play a key role in cell wall formation.

However, the molecular mechanism of inhibition remains unclear, thus hindering the design of new-generation drugs aimed at conquering drug resistance.

After six years of research, a joint team led by Rao Zihe, a professor from ShanghaiTech University, announced recently that they have discovered the three-dimensional structures of ethambutol targeted proteins and how the drugs act on them to inhibit formation Mycobacterium tuberculosis cell wall.

They also found at molecular level how drug resistance occurs by the mutations, which should be taken into consideration in new-generation drug design in order to solve the resistance problem.

Currently, the team is taking full advantage of the Zhangjiang Biomedical Industry Base (Shanghai) to push forward new anti-TB drug development.