Mode of action of the ecdysone agonist tebufenozide (RH-5992), and an exclusion mechanism to explain resistance to it

Arthur Retnakaran, Ivan Gelbic, Meenakshi Sundaram, William Tomkins, Tim Ladd, Mark Primavera, Qili Feng, Basil Arif, Reddy Palli, Peter Krell

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Spruce budworm larvae (Choristoneura fumiferana) upon ingesting tebufenozide (RH-5992) stop feeding and go into a precocious, incomplete molt, leading eventually to death. Like 20-hydroxyecdysone (20E), tebufenozide also acts at the receptor level and transactivates the expression of up-regulated genes but, because of its persistence, the down-regulated genes that are normally expressed in the absence of 20E are not expressed. While tebufenozide is lepidopteran-specific, an analog, RH-5849, is effective on dipterans. This is reflected in the respective effects of the two compounds on Cf-203 (C. fumiferana - 203), a lepidopteran cell line and Dm-2 (Drosophila melanogaster - 2), a dipteran cell line. Cf-203 cells accumulated [14C]tebufenozide and expressed CHR3 (Choristoneura hormone receptor 3), but Dm-2 cells excluded the material and did not express DHR3 (Drosophila hormone receptor 3). Using yeast ABC (ATP binding cassette) transporter mutants, we determined that PDR5 (pleiotropic drug resistance 5) was responsible for the exclusion. We discovered recently that older instars of the white-marked tussock moth (Orgyia leucostigma) are resistant to tebufenozide, perhaps as a result of such an exclusion system. We are currently cloning PDR5 (pleiotropic drug resistance 5), which is an essential step in studying the resistance mechanism.

Original languageEnglish
Pages (from-to)951-957
Number of pages7
JournalPest Management Science
Volume57
Issue number10
DOIs
StatePublished - 2001

Keywords

  • 20-hydroxyecdysone
  • ABC transporter
  • Choristoneura fumiferana
  • Ecdysone agonists
  • PDR5
  • Precocious molting
  • RH-5992
  • Tebufenozide
  • Yeast

ASJC Scopus subject areas

  • Agronomy and Crop Science
  • Insect Science

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