title: Differences in nicotine metabolism of two Nicotiana attenuata herbivores render them differentially susceptible to a common native predator.
abstract: BACKGROUND
  Nicotiana attenuata is attacked by larvae of both specialist (Manduca sexta) and generalist (Spodoptera exigua) lepidopteran herbivores in its native habitat. Nicotine is one of N. attenuata's important defenses. M. sexta is highly nicotine tolerant; whether cytochrome P450 (CYP)-mediated oxidative detoxification and/or rapid excretion is responsible for its exceptional tolerance remains unknown despite five decades of study. Recently, we demonstrated that M. sexta uses its nicotine-induced CYP6B46 to efflux midgut-nicotine into the hemolymph, facilitating nicotine exhalation that deters predatory wolf spiders (Camptocosa parallela). S. exigua's nicotine metabolism is uninvestigated.
  
  
  RESULTS
  We compared the ability of these two herbivores to metabolize, tolerate and co-opt ingested nicotine for defense against the wolf spider. In addition, we analyzed the spider's excretion to gain insights into its nicotine metabolism. Contrary to previous reports, we found that M. sexta larvae neither accumulate the common nicotine oxides (cotinine, cotinine N-oxide and nicotine N-oxide) nor excrete them faster than nicotine. In M. sexta larvae, ingestion of nicotine as well as its oxides increases the accumulation of CYP6B46 transcripts. In contrast, S. exigua accumulates nicotine oxides and exhales less (66%) nicotine than does M. sexta. Spiders prefer nicotine-fed S. exigua over M. sexta, a preference reversed by topical or headspace nicotine supplementation, but not ingested or topically-coated nicotine oxides, suggesting that externalized nicotine but not the nicotine detoxification products deter spider predation. The spiders also do not accumulate nicotine oxides.
  
  
  CONCLUSIONS
  Nicotine oxidation reduces S. exigua's headspace-nicotine and renders it more susceptible to predation by spiders than M. sexta, which exhales unmetabolized nicotine. These results are consistent with the hypothesis that generalist herbivores incur costs of detoxification, which include the ecological costs of greater predation risks, in addition to the previously demonstrated energetic, physiological and metabolic costs.
authors.affiliation: Department of Molecular Ecology, Max-Planck-Institute for Chemical Ecology, Jena, Germany.
authors.forename: Pavan
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Department of Molecular Ecology, Max-Planck-Institute for Chemical Ecology, Jena, Germany.
authors.forename: Preeti
authors.initials: P
authors.lastname: Rathi
authors.affiliation: Department of Molecular Ecology, Max-Planck-Institute for Chemical Ecology, Jena, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schöttner
authors.affiliation: Department of Molecular Ecology, Max-Planck-Institute for Chemical Ecology, Jena, Germany.
authors.forename: Ian T
authors.initials: IT
authors.lastname: Baldwin
authors.affiliation: Department of Molecular Ecology, Max-Planck-Institute for Chemical Ecology, Jena, Germany.
authors.forename: Sagar
authors.initials: S
authors.lastname: Pandit
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004790:Enzyme Induction; D006458:Hemolymph / Q000378:metabolism; D060434:Herbivory; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D007814:Larva / Q000378:metabolism; D018402:Manduca / Q000378:metabolism*; D009538:Nicotine / Q000378:metabolism*; D010084:Oxidation-Reduction; D011235:Predatory Behavior; D013112:Spiders / Q000502:physiology*; D018411:Spodoptera / Q000378:metabolism*; D014026:Nicotiana / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D019476:Insect Proteins; D009538:Nicotine; D003577:Cytochrome P-450 Enzyme System
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