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

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.

Seletividade de inseticidas usados na cultura da macieira a duas populações de Chrysoperla externa (Hagen, 1861) (Neuroptera: Chrysopidae)

“…Metoxifenozide e tebufenozide agem como mímicos do ecdisônio, induzindo o início do processo de ecdise, sendo considerados mais específicos para insetos da ordem Lepidoptera (CARLSON et al, 2001). Talvez, por essa característica, não tenham apresentado efeito prejudicial à sobrevivência das larvas de C. externa, conforme também constataram RETNAKARAN et al (2001) em parasitóides de lagartas pertencentes às ordens Diptera e Hymenoptera.…”

Chitin metabolism in insects: structure, function and regulation of chitin synthases and chitinases

“…The auxiliary application of isolated molting hormones or their synthetic agonists and antagonists leads to abnormalities in insect development as well. The ecdysteroid agonist tebufenozide manifests its effect by interacting with the ecdysone receptor, the juvenile hormone agonists fenoxycarb, methoprene and pyriproxyfen mimic the hormone action, and the juvenile hormone antagonists precocene I and II act via their cytotoxicities on the corpora allata (Schooneveld, 1979;Mulla et al, 1985;Dhadialla et al, 1998;Hoffmann and Lorenz, 1998;Kostyukovsky et al, 2000;Retnakaran et al, 2001).…”

Effects of nonsteroidal ecdysone agonist RH-5992 and chitin biosynthesis inhibitor lufenuron on Spodoptera littoralis (Boisduval, 1833)

“…RH-5992 has been shown to induce precocious molting in all tested lepidopteran larvae, including the tobacco hornworm, Manduca sexta, and the spruce budworm, Choristoneura fumiferana [5][6][7][8].…”