Dissection of Francisella virulence in a genetically tractable host system

Francisella is a dangerous pathogen that establishes infection in range of vertebrates and invertebrates. Some species, e.g. F. noatunensis have been shown to infect wild and farmed aquatic organisms causing damage and major economic losses. Little is kn own about their virulence mechanisms due to the complexity and low tractability of the laboratory systems which are used to study them, for example fish lines. Interestingly, several Francisella species have been shown to infect or persist in a symbiotic relationship with environmental amoeba. Dictyostelium discoideum is an amoeba that is very similar to immunecells of higher organisms and is well established to study basic cellular processes. In the laboratory of Dr. M. Hagedorn Dictyostelium is used as a host cell to study the mycobacteria virulence with Mycobacterium marinum, a natural fish pathogen and close relative of M. tuberculosis. Ass. Prof. Winther-Larsen has a longstanding expertise in molecular infection microbiology of both mammalian and fis h pathogens including construction of knock-out mutants of various Francisella species. We wanted to combine our complementing expertise to establish the amoeba Dictyostelium discoideum as a new, genetically tractable host cell to study Francisella virule nce mechanisms. During a 4-week visit E. Lampe a PhD student in Oslo, visited the BNI laboratory in 2012. She established in a collaboration with Hagedorn that Francisella is a pathogen of Dictyostelium. Furthermore, a genetically modified mutant of Franc isella made by E. Lampe did not cause disease in the Dictyostelium host. These preliminary experiments shows that Dictyostelium provide a host-cell system to study Francisella infections. We want to futher use this system to expand our knowledge and deepe r understanding of the course of Francisella infections. We want to continue collaborating and have initiated writing grants (EMBO, EU) to do so. The DAADppp grant would futher facilitate these efforts.