title: Chemosensation of bacterial secondary metabolites modulates neuroendocrine signaling and behavior of C. elegans.
abstract: Discrimination between pathogenic and beneficial microbes is essential for host organism immunity and homeostasis. Here, we show that chemosensory detection of two secondary metabolites produced by Pseudomonas aeruginosa modulates a neuroendocrine signaling pathway that promotes avoidance behavior in the simple animal host Caenorhabditis elegans. Secondary metabolites phenazine-1-carboxamide and pyochelin activate a G-protein-signaling pathway in the ASJ chemosensory neuron pair that induces expression of the neuromodulator DAF-7/TGF-β. DAF-7, in turn, activates a canonical TGF-β signaling pathway in adjacent interneurons to modulate aerotaxis behavior and promote avoidance of pathogenic P. aeruginosa. Our data provide a chemical, genetic, and neuronal basis for how the behavior and physiology of a simple animal host can be modified by the microbial environment and suggest that secondary metabolites produced by microbes may provide environmental cues that contribute to pathogen recognition and host survival.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Meisel
authors.affiliation: Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Oishika
authors.initials: O
authors.lastname: Panda
authors.affiliation: Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Parag
authors.initials: P
authors.lastname: Mahanti
authors.affiliation: Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Schroeder
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: dhkim@mit.edu.
authors.forename: Dennis H
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D017173:Caenorhabditis elegans / Q000235:genetics / Q000276:immunology* / Q000382:microbiology* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009490:Neurosecretory Systems / Q000502:physiology; D010619:Phenazines / Q000378:metabolism; D010636:Phenols / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D013045:Species Specificity; D013844:Thiazoles / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C102095:DAF-7 protein, C elegans; D010619:Phenazines; D010636:Phenols; D013844:Thiazoles; D016212:Transforming Growth Factor beta; C420923:phenazine-1-carboxamide; C025316:pyochelin