Compared to most other bacterial pathogens, M. tuberculosis has evolved a unique life style: it resides and multiplies in cells equipped to efficiently kill bacterial pathogens - the macrophages. After uptake by macrophages M. tuberculosis arrests phagosome maturation at the stage of an early endosome. Inhibition of phago-lysosome fusion is thought to be of major importance for intracellular survival of M. tuberculosis.

To investigate the molecular basis for host-pathogen interaction a combination of molecular, genetic, biochemical and cell biology techniques along with in-vivo investigations is used to study and characterize mechanisms involved in M. tuberculosis virulence and host defense. By targeted gene inactivation (Mol. Microbiol. 1995, 16: 991) defined isogenic mutants in genes involved in adhesion, nutrient uptake (Mol. Microbiol. 2002, 46: 191), signalling (Mol. Microbiol. 2005, 57: 6, Int. J. Med. Microbiol. 2006, 296(8):563) and protein processing (Mol. Microbiol. 2004, 52: 1543, Microbiology 2008, 154: 2991, Cell Host Microbe. 2008, 17;3(4):224)are generated and studied in different infection models. Attenuated mutants are further characterized at the cell biology level using live cell imaging, confocal laser scan microscopy, and electron microscopy to investigate intracellular trafficking.

• Project: Mycobacterium tuberculosis - mechanisms of virulence (P. Sander)