Researchers have discovered a new metabolic pathway in the
bacterium that causes tuberculosis (TB) in humans, which might help
it to obtain nutrients from its host, evade the immune system and
ultimately cause this deadly disease.
The research, by a team at the MRC's National Institute for
Medical Research (NIMR; now part of the Francis Crick
Institute), may open up a new avenue for TB treatment, by
finding antibiotics that specifically target this
pathway.
Dr Luiz Pedro de Carvalho of NIMR explained: "Novel drugs
against new targets are urgently needed to treat the increasing
spread of strains of Mycobacterium tuberculosis, the bacterium that
causes human TB, that are resistant to currently available
drugs.
"Validated targets for drug discovery are essential for the
successful development of new drugs. Therefore, our findings and
future experiments will be essential to the development of new
antibiotics targeting this unexplored
pathway."
Dr de Carvalho's team at NIMR worked with colleagues from the
University of Michigan in the USA to study previously unknown
proteins in the genome of M. tuberculosis and to investigate what
they do. They used a new screening method called 'metabolomic
profiling', which allows hundreds of metabolites to be separated,
identified and quantified simultaneously. The scientists then
carried out follow-up genetic, biochemical and structural studies
to confirm their findings.
They found an unexpected enzyme called glycerol phosphate
phosphatase (GPP), which led to the discovery of a previously
completely unknown metabolic pathway in M.
tuberculosis.
Dr de Carvalho said: "We are now evaluating the importance of
this GPP and its related metabolic pathway in experimental models
of infection. If the enzyme and pathway turn out to be important
for infection, this will open a new avenue for target-based
antibiotic discovery against M.
Tuberculosis."
"Our study highlights the abundance of enzymatic reactions and
biochemical pathways to be discovered, even in well characterised
pathogens such as M. tuberculosis."
The paper, Discovery of a glycerol3-phosphate phosphatase reveals
glycerophospholipid polar head recycling in Mycobacterium
tuberculosis, is published in the Proceedings of
the National Academy of Sciences.