Principal investigators: Astrid Lewin and Hubert Schäfer

The genus Mycobacterium (M.) includes important bacterial pathogens such as the causative agent of tuberculosis, M. tuberculosis or the leprosy pathogen, M. leprae. The mycobacteria also comprise more than 100 bacterial species which are termed nontuberculous mycobacteria (NTM) and can cause serious diseases, such as pulmonary infections, lymphadenitis in small children as well as skin, soft tissue and joint infections. The most important NTM pathogen in Germany is M. avium subsp. hominissuis, which can cause serious infections in particular in immunodeficient persons such as AIDS-patients. Another problematic pathogen is M. abscessus. This bacterium often causes lung infections in patients with cystic fibrosis that are extremely hard to treat.

Pathogenic mycobacteria are characterised by their ability to survive and multiply in macrophages. Furthermore, some of them are able to induce the formation of granulomas. These are structured aggregates of immune cells which limit the multiplication and dissemination of the bacteria. Within these granulomas mycobacteria can survive in a state of latency. In most industrial countries the number of infections with tuberculous mycobacteria has been decreasing over the last decades; the number of diseases caused by NTM however, seems to increase. For that reason there is a considerable need for research both on the pathogenicity of these bacteria and on the improvement of diagnostic and therapeutic approaches targeting these infections.

Within the scope of this project the mechanisms of action which allow mycobacteria to escape the defence mechanisms of the immune system are to be identified and characterised. To do so, we compare the genetic structure of different pathogens, identify virulence genes and investigate their impact on the interaction with host cells. A focus of our work is the characterization of the species M. avium and M. abscessus causing hardy lung infections especially in immune-compromised persons and in patients with cystic fibrosis.

On the other side of the interaction between pathogens and the host we try to identify and characterise the immune mechanisms which act at the defence against mycobacterial infections. In this context the immune reactions caused by an M. avium infection will be characterised. In parallel, the effector mechanisms are to be identified which impart a certain degree of protection against infections by mycobacteria after immunisation with the vaccine strain BCG (Bacille Calmette Guérin).

In a further approach we try to specifically identify the proteins of Mycobacterium avium hominissuis which trigger an immune response during an infection, i.e. act as immunodominant antigens. Knowledge about these antigens can contribute to an improvement of diagnostic measures or to developing new vaccines.

Co-workers:

Elisabeth Kamal, Gudrun Kliem, Barbara Kropp, Petra Matzk, Greana Kirubakar, Suriya Akter

Sub-projects:

• Isolation and characterization of NTM isolated from patients with cystic fibrosis
• Comparative analysis of the genome structure of M. avium isolates and M. abscessus isolates from patients and the environment
• Investigation of the interaction of different M. avium and M. abscessus isolates with human cells
• Isolation and characterisation of new virulence factors of M. avium and M. abscessus
• Investigation of the role of selected latency-associated genes of M. bovis BCG for the interaction with human cells
• Identification of immunogenic proteins from M. avium
• Characterisation of effector mechanisms at the immune response against mycobacteria