New research brings hope of stemming the TB tsunami

Professor Valerie Mizrahi, Director of the Institute of Infectious Disease and Molecular Medicine (IDM) and her research team have collaborated with international researchers in publishing four new papers on TB drug discovery that have generated considerable attention in the field. Professor Mizrahi and her research team are internationally recognised for their work on studying aspects of the physiology and metabolism of Mycobacterium tuberculosis (Mtb) relevant to TB drug discovery, as well as drug resistance.

In one of the recently-published studies, done under the auspices of the More Medicines for Tuberculosis (MM4TB) consortium funded by the European Commission, Mizrahi's group worked with collaborators in Switzerland, Italy, Hungary and the United Kingdom (UK) to identify and validate the enzyme GuaB2 as a new TB drug target. This study, led by postdoctoral fellow Dr Vinayak Singh, exemplifies the 'phenotypic' approach to TB drug discovery; which starts with finding a molecule that can inhibit the growth of the TB bacterium, and then figuring out how it works. In this case, MM4TB researchers – led by Stewart Cole from the École Polytechnique Fédérale de Lausanne, in Switzerland – identified a molecule (VCC234718) which could kill the Mtb TB bacterium, but showed limited toxicity against mammalian cells.

In a related study, team member Dr Joanna Evans in the IDM validated a component of Mtb's enzymatic machinery for producing the ubiquitous cofactor 'coenzyme A' as another new TB drug target. As in the GuaB2 study, this project, which was carried out under the TB Drug Accelerator programme funded by the Bill & Melinda Gates Foundation, involved international collaboration – this time with world-leading scientists from Weill Cornell Medical College and the National Institutes of Health (NIH), USA.

Collaborative work has benefited all team players, with research groupings within the IDM drawing on one another's experience and expertise, says Mizrahi. These include the MRC/NHLS/UCT Molecular Mycobacteriology Research Unit, which Mizrahi leads together with her colleague and IDM Associate Member Associate Professor Digby Warner; and others, such as UCT's H3D Centre for Drug Discovery and Development, led by IDM Member Professor Kelly Chibale.

Original article:
http://www.research.uct.ac.za/new-research-brings-hope-stemming-tb-tsunami#sthash.PU78HtGL.dpuf