The fight against tuberculosis (TB) and other lung diseases based on a better understanding of the causative agents is the central aim of our research. In the main focus are Mycobacterium tuberculosis complex strains (Mtbc) and other bacterial lung pathogens. The translational research agenda comprises the following topics: local and global transmission dynamics, determination of resistance and compensatory mechanisms, population structure and evolution of Mtbc strains and other mycobacteria, virulence/physiology/pathobiology of mycobacteria, application of high-throughput technologies in research and diagnostics, implementation of new technologies in high incidence countries, as well as for individualized therapy and evolutionary medicine. Whole genome sequencing (WGS) approaches are applied for high resolution characterization of pathogen genomes and for transcriptome studies.  More than 300 strains per weak are currently under investigation in our pathogenomic laboratory and overall, genome data of more than 15.000 Mtbc-strains and of other lung pathogens are available for downstream analyses. Key research is performed on the pathogens global population structure and the link between pathogen diversity, virulence properties and host-pathogen interaction. This work has laid the basis for an understanding of historic evolution and population structure of the tubercle pathogens. Even more importantly, it has linked this finding with Mtbs pathobiological diversity and the outcome of infection, thus pioneered investigations of the co-evolution and interaction of the pathogen and the host. In a complementary approach ranging from basic mycobacteriology, macrophage infection experiments to transcriptome profiling and host genetic studies, we aim to define mycobacterial virulence factors and their correlation with host genetics. Presently, we are exploring NGS based RNAseq strategies to get a deeper understanding of virulence mechanism of the pathogen, e.g. in stress models (infection models, dormancy, persister). These studies are critical for understanding the diverse outcomes of infection, individualized treatment efficacy, and the development of new personalized diagnostics and therapeutics.

CRyPTIC Consortium and the 100,000 Genomes Project (Beckert P, Kohl TA, Merker M, Niemann S, Utpatel C). Prediction of Susceptibility to First-Line Tuberculosis Drugs by DNA Sequencing. N Engl J Med 379(15):1403-1415 (2018).           

Merker M, Barbier M, Cox H, Rasigade JP, Feuerriegel S, Kohl TA, Diel R, Borrell S, Gagneux S, Nikolayevskyy V, Andres S, Nübel U, Supply P, Wirth T, Niemann S. Compensatory evolution drives multidrug-resistant tuberculosis in Central Asia. Elife 7. pii: e38200 (2018).

Kohl TA, Harmsen D, Rothgänger J, Walker T, Diel R, Niemann S. Harmonized Genome Wide Typing of Tubercle Bacilli Using a Web-Based Gene-By-Gene Nomenclature System. EBioMedicine 34:131-138 (2018).

Meehan CJ, Moris P, Kohl TA, et al., Niemann S*, de Jong BC*. The relationship between transmission time and clustering methods in Mycobacterium tuberculosis epidemiology. EBioMedicine 37:410-416 (2018). *equal contribution

van Ingen J*, Kohl TA*, Kranzer K*, et al., Spröer C, Bunk B, Nübel U, Bloemberg GV*, Böttger EC*, Niemann S*, Wagner D*, Sax H*. Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study. Lancet Infect Dis 17(10):1033-1041 (2017). *equal contribution

Walker TM*, Merker M*, et al., Niemann S*, Böttger EC*, Keller PM*; MDR-TB Cluster Consortium. A cluster of multidrug-resistant Mycobacterium tuberculosis among patients arriving in Europe from the Horn of Africa: a molecular epidemiological study. Lancet Infect Dis 18(4):431-440 (2018). *equal contribution