The bacterium, Pseudomonas aeruginosa, is capable of causing diseases in a wide range of plant and animal hosts. In particular, it is an opportunistic pathogen for humans and causes serious infections in individuals with Cystic Fibrosis, and those with other immunological deficiencies. Recent studies have shown that P. aeruginosa also behaves as a pathogen of the nematode, Caenorhabditis elegans. Specifically, the bacterium produces a toxin that quickly paralyzes the worm, leading to its death. Mutant worms can be isolated that are resistant to the toxin, and such mutations confer neuromuscular defects. The long-term objective of this study is to develop a model system for the study of host-pathogen interactions at the molecular genetic level. The proposed research addresses the following specific aims. 1) Two genetic screens are proposed to identify genes encoding the P. aeruginosa paralytic toxin. 2) The toxin will be purified and characterized by standard biochemical techniques. 3) The role of the Xcp protein secretion pathway in toxin production will be characterized. 4) Known C. elegans mutants with a variety of neuromuscular defects will be screened for resistance to the paralytic toxin. Such a screen should help elucidate the toxin's target and mechanism of action.
