“FHMS FESTIVAL OF RESEARCH - ONE HEALTH” University of Surrey 2017

Tuberculosis is a serious public disease, caused by Mycobacterium tuberculosis, and the emergence of multidrug resistant strains of the bacterium has greatly decelerated control of the disease.

There is an urgent need for new strategies to tackle this global emergency. Host-directed adjuvant therapies are a promising strategy to achieve improved therapy outcomes and reduce the lengthy treatment period for TB. Designing host directed therapies requires a comprehensive understanding of the pathogen induced mechanisms for hijacking the host cell machinery.

The manipulation of host cell gene expression plays a major role in the survival of pathogens inside the host cell. However there is lack of knowledge on the mechanisms involved in translational control. Here we show that M. tuberculosis induces a global reduction in translation in human macrophages which is mediated via the MAP kinase pathway. MAPK kinase arrays showed significant increased ERK phosphorylation, the protein that in turn activates Mnk, promoting therefore eIF4E phosphorylation and causing changes in host translational activity. eIF4E and mnk inhibitors are therefore promising targets for host-directed TB therapies.