|Liu, Zhiqi - MICHIGAN STATE UNIV.|
|Tan, Jianguo - MICHIGAN STATE UNIV.|
|Dong, Ke - MICHIGAN STATE UNIV.|
Submitted to: Insect Biochemistry and Molecular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 1, 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. Scientists at Michigan State University and the USDA-ARS (Center for Medical, Agricultural and Veterinary Entomology) recently sequenced the para gene from field populations of the German cockroach and identified two new mutations that increase the insensitivity of nerves to pyrethroid insecticides and enhance the knockdown resistance mechanism. To examine whether these mutations also enhance the effect of kdr-associated mutations identified in other insects, the scientists combined these modifying mutations with kdr mutations from other insect species. It was determined that the modifying mutations identified from the German cockroach further decreased nerve sensitivity of other insect kdr mutations. These results indicate that th novel mutations from the German cockroach are important modifiers of sensitivity to pyrethroid insecticides.
Technical Abstract: Pyrethroid insecticide resistance due to reduced nerve sensitivity, known as knockdown resistance (kdr), is linked to multiple point mutations in the para sodium channel gene. Previously we showed that two mutations (E434K and C764R) in the German cockroach Para channel protein greatly enhances the ability of the L993F mutation (a known kdr mutation) to reduce Para channel sensitivity to deltamethrin, a pyrethroid insecticide. Neither E434K nor C764R alone, however, alters Para channel sensitivity. To examine whether these two mutations also enhance the effect of kdr- associated mutations identified in other insects, we introduced a V to M mutation into the cockroach Para protein at the position that corresponds to the V412M kdr mutation in the Heliothis virescens Para protein. We found that the V409M mutation alone modified the gating properties of the cockroach Para channel and reduced channel sensitivity to deltamethrin by 10-fold. Combining the V409M mutation with either the E434K or C764K alon did not reduce the V409M channel sensitivity to deltamethrin further. However, the triple mutation combination (V409M, E434K and C764R) dramatically reduced channel sensitivity by 100-fold compared with the wild type channel. Our results suggest that the E434K and C764R mutations are important modifiers of Para channel sensitivity to pyrethroid insecticides and may be part of a unique low-affinity pyrethroid-binding site.