Using Dictyostelium to Study Infection by Legionella

Microbial pathogens have evolved in relation to their mammalian hosts and have developed strategies for colonization, invasion, and pathogenesis. These infections are highly specific, involving specific host targets and signaling pathways. Some of these strategies involve the induction of host responses to facilitate the growth of the pathogen. In this case, the host becomes an active participant in the infection process.

One strategy to study the interactions between a pathogen and its host is the use of genetically tractable host models to study infections by identifying resistant host mutants. This approach may aid us in understanding the molecular mechanisms of pathogenesis, which are conserved from Dictyostelium to humans. With this in mind, we tested whether Dictyostelium could be used as a host for the opportunistic pathogen Legionella pneumophila. As can be seen, dicty is an excellent host for Legionella replication. We are now involved in a series of genetic selections directed at isolating Dictyostelium mutants that are resistant to Legionella infection. The molecular genetic advantages of Dictyostelium allow us to isolate affected genes. In collaboration with the laboratories of Howard Shuman and Margaret Clarke , we are trying to identify the various factors that Legionella uses during the infection process.

It has been shown that Legionella utilizes the Autophagy pathway for replication within the cell. Because we have now identified Autophagy genes in Dictyostelium and obtained knock-outs, we can study Legionella infection and the involvement of Autophagy in its intracellular multiplication. We have shown that autophagy does not seem to be essential for Legionella pneumophila infection as was thought to be the case. For full article