Host immunity and intracellular efficacy of anti-tuberculosis drugs are essential for preserving the activity of novel drugs against tuberculosis

Multi drug resistant tuberculosis (MDR TB) caused by Mycobacterium tuberculosis (Mtb) affects 500 000 patients yearly with substantial mortality and is challenging even in a low incidence country like Sweden.

Overall, this project is evaluating the concept of a mycobacterium growth inhibition assay (MGIA) developed within the research group as a surrogate marker of host immunity along with the assessment of the intracellular activity of TB drug regimen of each individual patient.

Specifically, we will explore the variability in the MGIA response to virulent Mtb within and between healthy subjects and patients with active and latent TB.

The major research gap of how the interaction between intracellular killing in concert with anti-TB drugs will be addressed by exposure of peripheral blood mononuclear cells (PBMCs) to virulent Mtb with and without antibiotic combinations used as in current management of TB including MDR TB.

We will approach our aims using newly developed intracellular leucocyte models including from patents with TB infection along with live-cell microscopy in our research BSL3 laboratory enabling work with virulent mycobacteria.

The major research output expected is to define the most efficient use of novel anti-TB drugs such as bedaquiline and pretomanid and how to protect them from further resistance development.