Mapping the course of infection:
Dictyostelium to study mycobacteria and francisella infections
The amoeba Dictyostelium discoideum is a professional phagocyte, which is easily genetically and biochemically tractable. It is a well established-system to study basic cellular processes and, especially in recent years, established to investigate the
interactions between intracellular bacteria and their host cell.
In our laboratory we infect Dictyostelium with Mycobacterium marinum, a close relative of Mycobacterium tuberculosis and follow the course of infection. The arrest of phagosomal maturation is a key event in the establishment and maintenance of mycobacteria infection, however, the underlying molecular mechanisms are not well understood. In our recent work we could show that modulation of actin, which is present around the early replication compartment, reverses partially mycobacteriainduced phagosomal maturation arrest.
In addition, together with the Winther-Larsen laboratory (School of Pharmacy) we could show that the Francisella noatunesis ssp. noatunesis infects Dictyostelium and established Francisella virulence loci are conserved. These observations and especially the conservation of virulence mechanisms opens doors to establish a new model system to study the molecular mechanisms of a Francisella infection.
SELECTED PUBLICATIONS
Hagedorn M, Kyle H Rohde, David G Russell and Soldati T (2009) Infection by tubercular mycobacteria is spread by non-lytic ejection from their amoeba host. Science, 323(5922):1729
Hagedorn M and Soldati T (2007) Flotillin and RacH modulate the intracellular immunity of Dictyostelium to Mycobacterium marinum. Cell Microbiol, 9(12):2716.
Anes E, Peyron P, Staali L, Jordao L, Gutierrez MG, Kress H, Hagedorn M, Maridonneau Parini I, Skinner MA, Wildeman AG, Kalamidas SA, Kuehnel M, Griffiths G. (2006) Dynamic life and death interactions between Mycobacterium smegmatis and J774 macrophages. Cell Microbiol, 8(6):939.
Hagedorn M and Soldati T (2009) "Intracellular Niches of Pathogens - A Microbe's Guide through the Host Cell", Invited chapter on Mycobacterium marinum. Wiley-VCH Publisher, Editors: Prof. Dr. Schaible, Prof. Dr. Haas.