OR11

Tuberculosis is an ancient disease that has persisted through the ages and remains a significant global health challenge. Thus, a fundamental question arises: how have both host and pathogen managed to persist?

In this study we used the Drosophila melanogaster model to study the host-pathogen coevolution within the context of tuberculosis, using the closely related pathogen Mycobacterium marinum. We focused on dissecting the immune response mounted by the flies and the pathogen's evolving strategies for evasion.

We followed the infection over ten generations of Drosophila with each generation being reinfected by their own isolated pathogen. Furthermore, we exposed the flies to low doses of a heat-inactivated environmental mycobacterium, Mycolicibacterium manresensis, to assess the potential impact that presence of environmental mycobacteria might have to the host-pathogen coevolution. At generations 5 and 10, each group was infected with progressively increasing doses of M. marinum recovered from previously infected groups for the tolerance/resistance assays, aimed at determining whether there were changes in the virulence of M. marinum after coevolution with the host. We also used non-coevolved flies as control groups.

The results underscore the effectiveness of D. melanogaster as a model system for studying host-pathogen coevolution. Results showed that coevolved hosts increased their resistance to the infection with M. marinum, while the pathogen diminishes its virulence and its ability to thrive within the host. Moreover, the exposure to the heat-inactivated M. manresensis resulted in increased tolerance to the infection, as well as increased resistance, and an even stronger attenuation of the pathogen’s virulence.