Breakthrough in developing new antibiotic and vaccine for TB
18 October 2013
A French-British team has discovered that the tuberculosis bacterium can be prevented from growing by blocking a protein that transports the amino acid aspartate into the bacteria cell.
These results, published in the journal Nature Chemical Biology, could make it possible to develop new antibiotics that block this pathway and new vaccines derived from attenuated strains of the bacillus incapable of supplying themselves with aspartate.
The researchers discovered that aspartate is essential for the development of the tuberculosis bacteria, Mycobacterium tuberculosis, because it acts as its main source of nitrogen, a component of many molecules essential for life. They also established that a protein called AnsP1 transports aspartate from the host organism into the M. tuberculosis cell. The research team included scientists from CNRS, Inserm, the Institut Curie and Université Toulouse III - Paul Sabatier.
Tuberculosis, an infectious disease that generally affects the lungs and kills more than 1.5 million people each year throughout the world. A vaccine, BCG, is available against the bacillus but its efficacy is variable. Antibiotic treatments also exist, but doctors are increasingly confronted with strains that are resistant to several antibiotics, hence the need to develop new therapeutic and preventive strategies.
The researchers infected mice with a bacillus in which AnsP1 was inactivated. Surprisingly, this bacillus strain proved to be highly attenuated: it multiplied more slowly and caused much less damage than normal strains to the lungs of the mice. This highlights the unsuspected role of this aspartate transporter in the virulence of the mycobacterium.
AnsP1 and the other molecules involved in the metabolism of aspartate could therefore be potential targets for new antibiotics. Furthermore, this mutant strain in which AnsP1 has been inactivated could turn out to be a good candidate for the development of novel vaccines capable of providing better and longer protection than BCG.
Gouzy A, et al. Mycobacterium tuberculosis nitrogen assimilation and host colonization require aspartate. Nature Chemical Biology. Published online on 29 September 2013.