title: Lethal paralysis of Caenorhabditis elegans by Pseudomonas aeruginosa.
abstract: Identification of host factors that interact with pathogens is crucial to an understanding of infectious disease, but direct screening for host mutations to aid in this task is not feasible in mammals. The nematode Caenorhabditis elegans is a genetically tractable alternative for investigating the pathogenic bacterium Pseudomonas aeruginosa. A P. aeruginosa toxin, produced at high cell density under control of the quorum-sensing regulators LasR and RhlR, rapidly and lethally paralyzes C. elegans. Loss-of-function mutations in C. elegans egl-9, a gene required for normal egg laying, confer strong resistance to the paralysis. Thus, activation of EGL-9 or of a pathway that includes it may lead to the paralysis. The molecular identity of egl-9 was determined by transformation rescue and DNA sequencing. A mammalian homologue of EGL-9 is expressed in tissues in which exposure to P. aeruginosa could have clinical effects.
authors.affiliation: Department of Genetics, University of Washington, Seattle, WA 98195, USA.
authors.forename: C
authors.initials: C
authors.lastname: Darby
authors.forename: C L
authors.initials: CL
authors.lastname: Cosma
authors.forename: J H
authors.initials: JH
authors.lastname: Thomas
authors.forename: C
authors.initials: C
authors.lastname: Manoil
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000382:microbiology*; D029742:Caenorhabditis elegans Proteins; D002450:Cell Communication; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D004058:Diffusion; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010243:Paralysis / Q000235:genetics*; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C403074:Egl-9 protein, C elegans; D015801:Helminth Proteins; C080365:LasR protein, Pseudomonas aeruginosa; D011993:Recombinant Fusion Proteins; C086515:RhlR protein, Pseudomonas aeruginosa; D015534:Trans-Activators