project 6

the mechanism of protein secretion in pathogenic slow and fast growing mycobacteria

Project Leaders:
Matthias Wilmanns and Florian Maurer

Image proof:
Illustration: | © Infectophysics 2019

Mycobacteria are among the most threatening bacterial pathogens affecting humans both in the developing and developed parts of the world. Due to their extraordinary capacity to survive under hostile conditionals in the human host, mycobacterial infections especially of multi-drug resistant strains are difficult and occasionally even impossible to treat. The mycobacterial Type VII secretion system (T7SS) is a highly specialized molecular machine allowing to transport virulence proteins into host cells and thus is of central interest to understand pathogenesis. Our group has recently provided first structural insight into the underlying structure of this complex machine crossing the inner mycobacterial membrane (Beckham et al. Nature Microbiology, 2017). Apart from slow growing Mycobacterium tuberculosis (Mtb) causing tuberculosis, other more specialized, fast pathogenic mycobacteria are increasingly recognized to cause severe infections. M. abscessus (Mab) is a major cause for pulmonary infections in patients with chronic conditions such as cystic fibrosis. In this project, we aim at a comparative functional and structural characterisation of the T7SS of both Mab and Mtb to obtain an in-depth understanding of the role of these molecular complexes in the pathogenesis of mycobacterial infections. Due to the highly divergent expertise of the participating partners (integrative structural biology, biochemistry, genetics, microbiology, access to and diagnostic screening of patient samples) this project is ideally suited to unravel a broad understanding of the role of T7SS in mycobacterial pathogenicity and will thus provide a profound basis for future translational research.