|Tan, Jianguo - MICHIGAN STATE UNIV.|
|Liu, Zhigi - MICHIGAN STATE UNIV.|
|Tsai, Ti-Dao - PHARMACIA CORP.|
|Goldin, Alan - UNIV. OF CALIF., IRVINE|
|Dong, Ke - MICHIGAN STATE UNIV.|
Submitted to: Journal of Biological Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 15, 2001
Publication Date: N/A
Interpretive Summary: Knockdown resistance, or kdr, is an insecticide resistance mechanism caused by mutations in nervous system proteins of some insects. This mechanism often completely eliminates the effectiveness of pyrethroid and related insecticides against many insect species. Although the kdr mechanism has been reported in several German cockroach strains, the single mutation in the para gene, which has been repeatedly reported in kdr resistant insects does not always correlate with the presence or magnitude of knockdown resistance. Scientists at Michigan State University, Pharmacia Corporation, University of California, Irvine, and the USDA-ARS (Center for Medical, Agricultural and Veterinary Entomology) sequenced the para gene from recently collected field populations of German cockroach and identified four new mutations in the para gene. Two of these mutations were shown to further decrease nerve sensitivity to pyrethroid insecticides sin the German cockroach.
Technical Abstract: Pyrethroid insecticides alter the normal gating of voltage-gated sodium channels in the insect nervous system. Heavy use of pyrethroids has resulted in the selection of resistant populations in many insect species. Three para sodium channel mutations (E434K, C764R, L993F) were recently found to be associated with high-level pyrethroid resistance in the German cockroach (Blattella germanica). In this report, we show that the L993F mutation decreased Para channel sensitivity to the pyrethroid, deltamethrin, by 5-fold in Xenopus oocytes. In contrast, neither E434K nor C764R alone decreased channel sensitivity to deltamethrin. However, E434K or C764R combined with L993F reduced pyrethroid sensitivity by 100-fold. Furthermore, concomitant presence of all three mutations (KRF) reduced channel sensitivity to deltamethrin by 500-fold. None of the mutations significantly affected channel gating. However, sodium current amplitudes from the recombinant (not naturally occurring) Para channel carrying eithe E434K or C764R alone were much reduced compared to those of the wild-type channel or the channel carrying the naturally occurring double or triple mutations (KF, RF and KRF). These results suggest that high-level insensitivity to pyrethroids in the cockroach is achieved by sequential selection of the previously characterized L993F mutation and two novel para gene mutations, E434K and C764R.