The professional phagocyte Dictyostelium discoideum as a model host for bacterial pathogens

Abstract

The use of simple hosts such as Dictyostelium discoideum in the study of host pathogen interactions offers a number of advantages and has steadily increased in recent years. Infection-specific genes can often only be studied in a very limited way in man and even in the mouse model their analysis is usually expensive, time consuming and technically challenging or sometimes even impossible. In contrast, their functional analysis in D. discoideum and other simple model organisms is often easier, faster and cheaper. Because host-pathogen interactions necessarily involve two organisms, it is desirable to be able to genetically manipulate both the pathogen and its host. Particularly suited are those hosts, like D. discoideum, whose genome sequence is known and annotated and for which excellent genetic and cell biological tools are available in order to dissect the complex crosstalk between host and pathogen. The review focusses on host-pathogen interactions of D. discoideum with Legionella pneumophila, mycobacteria, and Salmonella typhimurium which replicate intracellularly.

Fig. (1). Infection of D. discoideum with different pathogens.

A) Transmission electron micrographs of L. pneumophila PhilI JR32 infected D. discoideum cells 3 and 48 hours post infection. 3 h after infection the host cell contains mostly one L. pneumophila (L) within the phagosome. After 48 h the D. discoideum cell is almost entirely filled with L. pneumophila. Scale bars, 2 µm. (Reproduced from figure 1 of [149], modified). B) Immunofluorescence micrographs of phase 2 of M. marinum infection of D. discoideum. Four sequential stages can be distinguished in the establishment and rupture of the vacuolin-positive vacuole. At the early stage 1, a single mycobacterium deformed a vacuole already enriched in vacuolin (black arrowheads). The second stage is defined by the proliferation of the bacteria inside the vacuole which leads to more deformation of the membrane (black arrowhead). At the late stages 3 and 4, the vacuolin-positive membrane was ruptured (arrowheads mark the edges of the membrane sheets generated during niche rupture) and bacteria were released into the cytosol (arrows). M. marinum is labelled in red and vacuolin in green. The scale bar represents 5 µm (Reproduced from figure 3 of [121], modified).