Final Report Summary - NEWTBDRUGS (New drugs for persistent tuberculosis: Exploitation of 3-D structure of novel targets, lead optimisation and functional in-vivo evaluation)
New strategies are urgently needed for combating the problems of TB treatment. NEWTBDRUGS have made four scientific breakthroughs, which indicate that it is feasible to develop such a drug:
1. As part of a post-genomic, interdisciplinary research project supported by the EC, we have recently solved the three-dimensional (3-D) structure of several, persistence related drug targets of MTB. NEWTBDRUGS have obtained information on ligands for these targets.
2. Their work has shown that persistent MTB is metabolically active, and so it should be susceptible to specific chemotherapy, albeit different from current antibiotics.
3. New assays have been developed which have been used for screening drugs, which kill persistent MTB. These assays can distinguish between drugs such as Isoniazid, which have little action against persisters, and compounds, which are known to have some anti-persister activity such as pyrazinamide.
4. They have identified unique compounds, which kill MTB including Rifampicin resistant strains.