OR36

1:Universidade do Porto

Infections by non-tuberculous mycobacteria (NTM), notably M. avium (Mav) and M. abscessus (Mab), have been notoriously increasing worldwide. Mab is currently one of the most challenging human pathogens, often called an “incurable nightmare”. There are no approved drugs specifically for this bacterium. NTM primarily affect immunocompromised patients, as well as individuals with underlying pulmonary diseases like cystic fibrosis. NTM disease requires long, multi-drug treatments that are often associated with poor patient compliance and low success rates. New and more effective treatments are urgently needed. One of the challenges associated with the development of new anti-NTM drugs is the lack of good in vitro and pre-clinical models, with a good capacity to predict clinical activity.

We recently created Mav and Mab reporter strains, for use in drug screening and development. The use of these strains simplifies the screening process, representing a significant advancement from CFU-based methods. With these strains, we created a drug development pipeline, including high throughput axenic and intra-macrophagic assays, as well as biofilm and organoid models. Moreover, we demonstrated that they can be used in vivo, either in larvae or mouse infection models.

Our experimental setting has already been successfully used to identify promising hits from available drug libraries. We are now working on testing these hits on the most complex infection models. The setting can also be used for compound optimization, mechanistic and PK/PD studies, representing a valuable asset for drug discovery against NTM.