title: A genome-wide screen of bacterial mutants that enhance dauer formation in C. elegans.
abstract: Molecular pathways involved in dauer formation, an alternate larval stage that allows Caenorhabditis elegans to survive adverse environmental conditions during development, also modulate longevity and metabolism. The decision to proceed with reproductive development or undergo diapause depends on food abundance, population density, and temperature. In recent years, the chemical identities of pheromone signals that modulate dauer entry have been characterized. However, signals derived from bacteria, the major source of nutrients for C. elegans, remain poorly characterized. To systematically identify bacterial components that influence dauer formation and aging in C. elegans, we utilized the individual gene deletion mutants in E. coli (K12). We identified 56 diverse E. coli deletion mutants that enhance dauer formation in an insulin-like receptor mutant (daf-2) background. We describe the mechanism of action of a bacterial mutant cyaA, that is defective in the production of cyclic AMP, which extends lifespan and enhances dauer formation through the modulation of TGF-β (daf-7) signaling in C. elegans. Our results demonstrate the importance of bacterial components in influencing developmental decisions and lifespan in C. elegans. Furthermore, we demonstrate that C. elegans is a useful model to study bacterial-host interactions.
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Khanna
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, USA.
authors.forename: Jitendra
authors.initials: J
authors.lastname: Kumar
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, USA.
authors.forename: Misha A
authors.initials: MA
authors.lastname: Vargas
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, USA.
authors.forename: LaKisha
authors.initials: L
authors.lastname: Barrett
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, USA.
authors.forename: Subhash
authors.initials: S
authors.lastname: Katewa
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Li
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, USA.
authors.forename: Tom
authors.initials: T
authors.lastname: McCloskey
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Naudé
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Nelson
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Brem
authors.affiliation: Nutrition &Metabolism Center, Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Killilea
authors.affiliation: Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Sean D
authors.initials: SD
authors.lastname: Mooney
authors.affiliation: Department of Metabolism &Aging, The Scripps Research Institute- Scripps Florida, Jupiter, Florida, 33458, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Gill
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, USA.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Kapahi
mesh_terms: D000375:Aging; D000818:Animals; D017173:Caenorhabditis elegans / Q000382:microbiology*; D048168:Escherichia coli K12 / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D055106:Genome-Wide Association Study