Pathogenesis and new therapeutic targets in drug-resistant tuberculosis (TB): Path-to-Resist-TB

Multidrug-resistant tuberculosis (MDR-TB) is a serious global health problem resulting from inappropriate antibiotic treatment of pulmonary TB, which highlights the need for new drug regimens.

In the project, Path-to-Resist-TB, we aim to join forces in the fight against antimicrobial resistance to increase the understanding of pathogenesis in patients with MDR-TB (Aims 1-2) and discover novel compounds with efficacy against drug-resistant mycobacteria (Aims 3-4).

Cells and immune pathways in tissue biopsies from MDR-TB lungs will be studied using multiplex spatial protein profiling that allows for detailed visualization of host-pathogen interactions in diverse microenvironments with high resolution.

We will also explore the diversity of the gut-lung microbiome and the effects on systemic inflammation after second-line MDR-TB therapy.

In parallel, we will explore novel molecules with either direct anti-mycobacterial effects or indirect effects on host immunity.

For this work, we will exploit a macrophage infection model and organotypic lung tissue model as well as relevant panels of disease-causing strains including MDR-TB and inherently drug-resistant non-tuberculous mycobacteria (NTM) using high-content imaging assays.

The results will promote identification of pathogenic mechanisms and novel antimicrobial agents that will pave the way for development of alternative treatment options for difficult-to-treat TB patients and prevent the spread of drug-resistance in the society.