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
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.