During the past few years, our laboratory and others have focused on the development of pathogenicity models using C. elegans as the host because of the extensive genetic and genomic resources available and because of the relative ease of identifying C. elegans mutants that exhibit altered susceptibility to pathogen attack. For example, several C. elegans mutants have been identified that exhibit enhanced susceptibility or enhanced resistance to killing by the human opportunistic pathogen Pseudomonas aeruginosa [M.-W. Tan, G. Alloing, R. Feinbaum and F. M. Ausubel, unpublished data]. In addition, we demonstrated that the highly specialized vertebrate pathogen Salmonella enterica serovar typhimurium is capable of killing C. elegans . When C. elegans is placed on a lawn of S. typhimurium , the bacteria accumulate in the lumen of the worm intestine and the nematodes die over the course of several days. The worms die with similar kinetics when placed on a lawn of S. typhimurium for a relatively short time (3-5 hours) before transfer to a lawn of E. coli . In contrast to P. aeruginosa , a small inoculum of S. typhimurium can proliferate in the C. elegans intestine and establish a persistent infection. Genetic analyses of S. typhimurium indicate that many virulence factors are important for both mammalian nematode pathogenesis. Despite the differences between the P. aeruginosa -mediated killing and the S. typhimurium -mediated killing, some of the C. elegans mutants more susceptible to P. aeruginosa turned out to be more susceptible to S. typhimurium , suggesting that some of the mechanisms underling host defense responses in C. elegans might be required to fight against bacterial infections in general. Also, we found that S. typhimurium colonization of the C. elegans intestine leads to an increased level of cell death in the worm gonad. Using a variety of C. elegans mutants in which cell death is blocked, we observed that S. typhimurium -induced germline cell death is dependent on the
ced-3 /
ced-4 cell death pathway. Moreover,
ced-3 and
ced-4 mutants are hypersensitive to S. typhimurium -mediated killing. These results suggest that PCD may be involved in the C. elegans defense response to pathogen attack.