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.

Highlights

  • D. discoideum is a fascinating member of the amoebozoa, whose natural habitat is deciduous forest soil and decaying leaves, where the amoebae feed on bacteria and yeast and grow as separate, independent, single cells

  • D. discoideum is suited for infection studies, because it is a professional phagocyte, its genome is completely sequenced and excellent genetic, biochemical and cell biological tools are available [2, 8, 10, 11]

  • D. discoideum was used to study the host response upon infection with different pathogens in particular L. pneumophila, M. marinum and M. avium and S. typhimurium. This led to the discovery of a variety of bacterial and host cell factors, among them many genes encoding cytoskeletal and signaling proteins that are important in the infection process

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Summary

INTRODUCTION

D. discoideum is a fascinating member of the amoebozoa, whose natural habitat is deciduous forest soil and decaying leaves, where the amoebae feed on bacteria and yeast and grow as separate, independent, single cells. The organism offers unique advantages for studying fundamental cellular processes with powerful molecular genetic, biochemical, and cell biological tools [2]. As a soil amoeba and a phagocyte D. discoideum can be a natural host of opportunistic bacteria and may have developed strategies to avoid invasion by given pathogens or to counteract their intracellular survival and replication [10,11,12]. Phagocytosis is a very complex, evolutionarily conserved mechanism that is used by higher eukaryotes to clear dead cells and cell debris and to counter the constant threat posed by pathogens For this purpose they harbour specialized cells such as macrophages, neutrophils or dendritic cells that have the ability to rapidly and efficiently internalize a variety of organisms and particles and degrade them. In recent years it became clear that the basic mechanisms of host pathogen interactions are

DISCOIDEUM AS EXPERIMENTAL SYSTEM FOR DRUG TESTING
CONCLUSIONS

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