Mechanisms of resuscitation as possible virulence mechanisms of clinical Mycobacterium tuberculosis isolates

• Applicant: Professor Dr. Stefan Niemann
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2013 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 248679813

The dimension of the global tuberculosis (TB) epidemic with more than 9 million new cases, two million deaths, and the emergence of multi drug resistant or extensively drug resistant clearly illustrates that an improved knowledge of the pathobiology is urgently needed to develop new concepts to combat TB more successfully in future. One key event in the pathogenesis of TB is that the pathogens of the Mycobacterium tuberculosis complex (MTBC) mainly go into a state of "latency/dormancy" directly after infection and approx. 10% of the infected cases progress to disease with subsequent transmission of the pathogens. Little is known about the factors that promote the resuscitation of the pathogens. Clearest evidence is that so called resuscitation promoting factors (Rpfs) are involved, however, their effect on clinical isolates has only poorly been investigated. In this study, we will carry out for the first time an in depth investigation of the effect of different Rpfs on a diverse collection of clinical MTBC isolates from different phylogenetic lineages in dormancy model systems. Transcriptome profiling will be used to define the factors involved in the resuscitation process. The significance of a selection of targets identified will be investigated by generation of knockout mutants and functional analyses. It is expected that the project will identify genes and gene products which are key players for the virulence of the MTBC and allow the bacteria to exploit dormant and persistent states to survive the host defence.

• DFG Programme: Research Grants