Lethal paralysis of Caenorhabditis elegans by Pseudomonas aeruginosa

Identification of host factors that interact with pathogens is crucial to a n understanding of infectious disease, but direct screening for host mutati ons to aid in this task is not feasible in mammals. The nematode Caenorhabd itis elegans is a genetically tractable alternative for investigating the p athogenic bacterium Pseudomonas aeruginosa. A P. aeruginosa toxin, produced at high cell density under control of the quorum-sensing regulators LasR a nd RhlR, rapidly and lethally paralyzes C. elegans. Loss-of-function mutati ons in C. elegans egl-9, a gene required for normal egg laying, confer stro ng resistance to the paralysis. Thus, activation of EGL-9 or of a pathway t hat includes it may lead to the paralysis. The molecular identity of egl-9 was determined by transformation rescue and DNA sequencing. A mammalian hom ologue of EGL-9 is expressed in tissues in which exposure to P. aeroginosa could have clinical effects.