[
Immunogenetics,
2000]
Toll receptor systems play an important role in our innate immune response to microbial infection (Rock et al. 1998). Studies of related pathways in arthropods (Hoffmann et all. 1999; Imler and Hofmann 2000) have led to key advances in our understanding of these processes. Until recently, however, the possibility that Toll signals may activate both immune and/or developmental pathways in Caenorhabditis elegans has been largely ignored. Early failures to identify Toll receptors or NFB-like transcription factors in the C. elegans genome (Ruvkun and Hobert 1998) let to the assumption that its Toll pathway was inoperable. Therefore, given the paucity of knowledge on innate immune responses for these animals, there was no impetus to develop C. elegans pathogenicity models. Recent database searches, however, have identified components of the elusive C. elegans Toll receptor pathway (Rich et al. 2000; Tan et al. 1999). The existence of a rudimentary immune response is further supported by evidence that antimicrobial peptides are encoded within the C. elegans genome (Tan and Ausubel 2000). In fact, C. elegans is susceptible to infection from several different pathogens, making this genetically tractable invertebrate an attractive model to study host-pathogen interactions. These developments are particularly important for the study of pathogens such as Pseudomonas aeruginosa whose natural hosts include humans. A suitable C. elegans model could, for example, provided a rapid system to screen candidate antibacterial drugs. Consequently, it has now become important to identify and isolate cDNAs for each component of the C. elegans Toll pathway.
Kurz CL, Ferrandon D, Andres E, Finlay BB, Uh M, Chauvet S, Hoffmann JA, Gorvel JP, de Bentzmann S, Vallet I, Steinmetz I, Aurouze M, Ewbank JJ, Michel GPF, Celli J, Filloux A
[
EMBO J,
2003]
The human opportunistic pathogen Serratia marcescens is a bacterium with a broad host range, and represents a growing problem for public health. Serratia marcescens kills Caenorhabditis elegans after colonizing the nematode's intestine. We used C. elegans to screen a bank of transposon-induced S. marcescens mutants and isolated 23 clones with an attenuated virulence. Nine of the selected bacterial clones also showed a reduced virulence in an insect model of infection. Of these, three exhibited a reduced cytotoxicity in vitro, and among them one was also markedly attenuated in its virulence in a murine lung infection model. For 21 of the 23 mutants, the transposon insertion site was identified. This revealed that among the genes necessary for full in vivo virulence are those that function in lipopolysaccharide (LPS) biosynthesis, iron uptake and hemolysin production. Using this system we also identified novel conserved virulence factors required for Pseudomonas aeruginosa pathogenicity. This study extends the utility of C. elegans as an in vivo model for the study of bacterial virulence and advances the molecular understanding of S. marcescens pathogenicity.