Salmonella typhimurium proliferates and establishes a persistent infectionin the intestine of Caenorhabditis elegans

Genetic analysis of host-pathogen interactions has been hampered by the lac k of genetically tractable models of such interactions. We showed previousl y that the human opportunistic pathogen Pseudomonas aeruginosa kills Caenor habditis elegans, that P. aeruginosa and C. elegans genes can be identified that affect this killing, and that most of these P. aeruginosa genes are a lso important for mammalian pathogenesis. Here, we show that Salmonella typ himurium as well as other Salmonella enterica serovars including S. enterit idis and S. dublin can also kill C. elegans. When C. elegans is placed on a lawn of S. typhimurium, the bacteria accumulate in the lumen of the worm i ntestine and the nematodes die over the course of several days. This killin g requires contact with live bacterial cells. The worms die with similar ki netics when placed on a lawn of S. typhimurium for a relatively short time (3-5 hours) before transfer to a lawn of E. coil. After the transfer to E. coil, a high titer of S. typhimurium persists in the C. elegans intestinal lumen for the rest of the worms' life. Furthermore, feeding for 5 hours on a 1:1000 mixture of S. typhimurium and E. coli followed by transfer to 100% E. coil, also led to death after several days. This killing correlated wit h an increase in the titer of S. typhimurium in the C. elegans lumen, which reached 10,000 bacteria per worm. These data indicate that, in contrast to P. aeruginosa, a small inoculum of S. typhimurium can proliferate in the C . elegans intestine and establish a persistent infection. S. typhimurium mu tated in the PhoP/PhoQ signal transduction system caused significantly less killing of C. elegans.