Tuberculosis still kills nearly 2 millions individuals every year on the global level, and new treatments are needed in complement to the current antibiotic regimen.
Claude Gutierrez in the team of Olivier Neyrolles at IPBS has discovered a novel “toxin-antitoxin” system in the tuberculosis bacillus, Mycobacterium tuberculosis. In this system, the toxin MbcT kills the bacillus if it is not neutralized by the antitoxin MbcA. In collaboration with the groups of Matthias Wilmanns (EMBL, Hamburg, Germany) and Luiz de Carvalho (The Francis Crick Institute, London, UK), the researchers found that MbcT degrades NAD+, a small molecule essential to life, through an unprecedented enzymatic reaction, that is NAD+ phosphorolysis. When artificially induced during infection, MbcT can kill M. tuberculosis with the same efficacy as that of other antimycobacterial drugs. This discovery paves the way for the search of novel anti-tuberculous compounds able to dislocate the MbcT-MbcA complex or to degrade MbcA, which should lead to the release of MbcT in the mycobacterial cytosol.