oa Editorial [Hot Topic: Model Organisms to Study Host - Pathogen Interaction: Prerequisites for the Identification of Novel Drug Targets (Guest Editor: Ludwig Eichinger)]

In the early nineties of the last century the possibility that human pathogens can be investigated in simple hosts was either not seriously taken into consideration or even denied by most researchers. Pioneering work in Frederick Ausubel's lab paved the way for the use of surrogate hosts in the study of host - pathogen interactions [1]. In retrospect it is not surprising that the investigation of host - pathogen interactions is possible in simple, non-natural hosts since underlying fundamental cellular processes are conserved from yeast to man. Likewise, many of the involved genes and their functions are conserved. The identification and analysis of crucial host or pathogen factors in non-natural hosts lead to a better understanding of the complex cross-talk between host and pathogen. Identified proteins may also constitute potential new antimicrobial drug targets and must then, preferably in the natural host, be further validated. In this special issue the use of eight model organisms to study host - pathogen interactions are described. Acanthamoebae are free-living amoebae and among the most prevalent protozoa found in the environment. They feed on bacteria by phagocytosis, however, some bacteria are able to survive and multiply within the amoebae. The intracellular growth of bacteria has been associated with enhanced environmental survival of the bacteria, increased virulence and decreased sensitivity to antibiotic substances (Sandstrom et al., this issue). The potential of the professional phagocyte Dictyostelium discoideum as an alternative model to higher organisms for host-pathogen interaction studies is discussed in the second review. Because hostpathogen 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 Dictyostelium, 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 (Bozzaro and Eichinger, this issue). The use of the model plant Arabidopsis thaliana accelerated our understanding of different plant-parasite interactions. Meanwhile hundreds of genes are known that are involved in different defence reactions, offering many new targets for drug development. Since some pathogenic strategies are conserved between animal and plant pathogens, results obtained with the plant system might be applicable to the animal system (Schlaich, this issue). The manuscript “C. elegans: an all in one model for antimicrobial drug discovery” aims at presenting the potential of the invertebrate Caenorhabditis elegans as an alternative model to mammalian systems for host-pathogen interaction studies. The advantages and limitations of this nematode for in vivo antimicrobial drug screenings and recent developments as well as perspectives concerning high-throughput approaches are discussed (Squiban and Kurz, this issue). Drosophila melanogaster whose basal immune response is well understood is a widely used model organism to decipher host-pathogen interactions. The review by Limmer et al. focuses mainly on infections with two categories of pathogens, the well-studied Gram-negative bacterium Pseudomonas aeruginosa and infections by fungi of medical interest. These examples provide an overview over the current knowledge on Drosophila-pathogen interactions and illustrate the approaches that can be used to study these interactions (Limmer et al., this issue). In vivo imaging in combination with advanced tools for genomic and large scale mutant analysis is one of the strengths of the zebrafish. The organism offers excellent possibilities as a high-throughput drug screening model for immune-related diseases, including inflammatory and infectious diseases and cancer. The review by Meijer and Spaink discusses the current knowledge on receptors and downstream signaling components that are involved in the zebrafish embryo's innate immune response and summarizes recent insights gained from the use of bacterial infection models, particularly Mycobacterium marinum (Meijer and Spaink, this issue). The guinea pig model of disease has been considered synonymous with the experimental laboratory animal since the nineteenth century. In the review by Anthony Hickey the use of the guinea pig as a laboratory animal, aspects of immunology, viral pathogens and host - pathogen models are discussed (Hickey, this issue). Mouse animal models, which mimic human disease, are invaluable tools for understanding the mechanisms of disease pathogenesis and the development of treatment strategies. The review by Herrero et al. describes the application of mouse animal models of alphaviral diseases to better understand the mechanisms that contribute to disease and to define the role that the immune response may have on disease pathogenesis with the view of providing the foundation for new treatments (Herrero et al., this issue). In summary, the manuscripts of this special issue highlight the potential of the different model organisms, from Acanthamoeba to Mouse, to dissect host - pathogen interactions and to unravel novel drug targets.