
One third of the world's overall population is infected with Mycobacterium tuberculosis (Mtb), the causing agent of Tuberculosis (TB). About 95% of those, are thought to be in latent infection where Mtb rarely replicates. Nevertheless, ~10% of latent infections eventually progresses to active disease, which, if left untreated, kills more than half of the infected patients. Mtb infection is best described as an equilibrium involving a balance of activation and suppression of host responses, orchestrated by a complex and dynamic series of interactions between multiple host and bacterial components. Therefore, it is not unsurprising that single-target approaches for the identification of lead compounds, followed by establishment of pipelines for drug discovery, have had limited success. To address such limitation, we plan to apply genome-wide approaches to characterize the mode-of-action of a compound library, which has been validated for its activity against Mtb by GlaxoSmithKline, a major player in the pharmaceutical industry. Our approach uses an alternative and highly promising route by starting rather than finishing an initial process for lead compound characterization.
The GeMoA consortium, composed by four academic research groups and one company from three European countries are joining efforts with the broad aim of integrating computational and experimental approaches into an innovative platform for genome-wide characterization of the mechanism-of-action for selected chemical compounds with activity against Mtb. Our teams will combine medicinal chemistry, synthetic chemistry, computational chemistry, computational biology, genomics, transciptomics, X-ray crystallography and biochemistry to address the need for identifying new targets and compounds that can lead to unexplored new mode-of-action against Mtb. We believe that the interdisciplinary combination of such expertises will indeed add value to our research and warrant higher chances of success than any of the isolated individual efforts that form the consortium.