For the first time, scientists have discovered how the
bacterium that causes tuberculosis (TB) takes up nitrogen, a
nutrient that is crucial for it to replicate, infect people and
spread.
The research may help in the development of new drugs to fight
this devastating illness.
Gérald Larrouy-Maumus and Luiz Pedro de Carvahlo of the MRC's
National Institute for Medical Research (now part of the
Francis Crick Institute) worked with colleagues from
the University of Toulouse, the Institute of Pharmacology and
Structural Biology at the National Centre for Scientific Research
and INSERM, all in France.
Dr de Carvahlo explained: "Nitrogen is a key element for
nutrition and is present in almost all biological molecules, such
as amino acids, which make up proteins, nucleosides, which make up
DNA and RNA and vitamins. This means that Mycobacterium
tuberculosis needs to take up nitrogen from the human host, its
sole natural reservoir."
Until now, it has been unclear what this source of nitrogen is
or what transport systems the bacterium uses for nitrogen uptake.
An improved understanding of the metabolic requirements of M.
tuberculosis during infection of a host may offer new targets for
treatments against the disease in the future.
For their study, the team combined classic genetics and
bacterial physiology methods with newer imaging techniques and
'metabolomic profiling' (see box) to investigate the role of a
protein called AnsP1, which they discovered was a transporter for
the amino acid aspartate. The scientists found that AnsP1 plays a
key role in acquisition of nitrogen by the bacteria, and is
important during infection. Together, the results indicate that
aspartate is a primary source of nitrogen for M. tuberculosis.
Dr de Carvahlo said: "Until this study, no one knew what
nitrogen sources were being used by M. tuberculosis during
infection of a human host. This study provides the first evidence
for how M. tuberculosis obtains nitrogen, as aspartate, from its
host.
"The validation of essential genes, such as those required
during infection, is a key step towards target-based drug
discovery. As we now understand the importance of aspartate and
AnsP1 during infection, we can try to develop drugs that block this
transporter, with the ultimate aim of treating tuberculosis."
The paper, Aspartate is required for Mycobacterium tuberculosis nitrogen
assimilation and host colonization, is published inNature Chemical Biology.