Negative cross-resistance of a pyrethroid-resistant Drosophila mutant to Phryma leptostachya-derived haedoxan A

Authors: QIE, XINGTAO - Northwest A&f University; Du, Yuzhe - Cathy; AIOUB, AHMED A. A. - Zagazig University; DONG, KE - Duke University; HU, ZHAONONG - Northwest A&f University

Submitted to: Insect Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/14/2021
Publication Date: 9/21/2021
Citation: Qie, X., Du, Y., Aioub, A., Dong, K., Hu, Z. 2021. Negative cross-resistance of a pyrethroid-resistant Drosophila mutant to Phryma leptostachya-derived haedoxan A. Insect Science. https://doi.org/10.1111/1744-7917.12973.
DOI: https://doi.org/10.1111/1744-7917.12973

Interpretive Summary: Pyrethroids are widely used as effective insecticides against agriculture pests However, the development of insect resistance to pyrethroids has markedly curtailed the effective use of pyrethroids in pest control and highlights the urgent need for alternative strategies in the management of insect resistance. Botanical insecticides, their extracts or metabolites derived from plants have been found to show notable insecticidal activities, such as Haedoxan A (HA). In this study, we conducted bioassays and reported a negative cross-resistance (NCR) between HA and permethrin in a pyrethroid-resistant Drosophila line, parats1, and found that although both parats1 larvae and adults were more resistant to permethrin, but more sensitive to HA compared with individuals of the susceptible line w1118 .NCR is generally considered a useful and cost-effective tool for pest resistance management, and the underlying molecular mechanisms of the NCR were studied. Our identification of the NCR between permethrin and HA sheds new light on the mode of action of HA.

Technical Abstract: Voltage-gated sodium channels are the primary target of pyrethroid insecticides. Mutations in sodium channel confer knockdown resistance (kdr) to pyrethroids in various arthropod pests. Haedoxan A (HA) is the major insecticidal component from Phryma leptostachya. It has been shown that HA alters electrical responses at the Drosophila neuromuscular junction and modifies the gating properties of cockroach sodium channels expressed in Xenopus oocytes. However, whether sodium channel mutations that confer pyrethroid resistance also affect the action of HA is unknown. In this study, we conducted bioassays using HA and permethrin in two Drosophila melanogaster strains: w1118, an insecticide-susceptible strain, and parats1, a pyrethroid-resistant strain due to a I265N mutation in the sodium channel, and identified a new case of negative cross-resistance (NCR) between permethrin and HA. Both parats1 larvae and adults were more resistant to permethrin, as expected. However, both parats1 larvae and adults were more sensitive to HA compared to w1118.We confirmed that the I265N mutation reduced the sensitivity to permethrin of a Drosophila sodium channel variant, DmNav22, expressed in Xenopus oocytes. Interestingly, the I265N mutation also abolished the effect of HA on sodium channels. Further characterization showed that I265 on the sodium channels is critical for the action of both pyrethroids and HA on sodium channels, pointing to an overlapping mode of action between pyrethroids and HA on the sodium channel. Overall, our results suggest an I265N-independnt mechanism(s) in parats1 flies that is responsible for the NCR between permethrin and HA at the whole insect level.