A potential lignan botanical insecticide from Phryma leptostachya against Aedes aegypti: laboratory selection, metabolic mechanism, and resistance risk assessment

The development of resistance to mosquitocides highlights the need for new insecticides that can be incorporated into a rational resistance management strategy. Botanical insecticides that are highly effective and safe to non-target organisms have recently gained attention. Haedoxan A (HA) is a lignan isolated from Phryma leptostachya L. that exhibits high activity against mosquito larvae. In the present study, we subjected Waco mosquitoes, a susceptible Aedes aegypti (L.) line, to selection with HA to investigate the insecticidal properties of HA and the mechanisms underlying the development of HA resistance. The resistance ratio achieved by third instar larvae from the HA-resistant (HAR) line at G 19 was 20.354-fold higher than that of the Waco line. Synergist tests showed that the HAR line developed resistance mainly via enhanced cytochrome P450-dependent monooxygenase activity. The realized heritability of resistance to HA in Ae. aegypti was 0.159. Resistance risk assessment indicated that 18 generations of Ae. aegypti are required for a tenfold increase in the LC 50 in real-world HA application. Moreover, HA had very low cross-resistance with imidacloprid and chlorpyrifos in the HAR line compared with the Waco line. Therefore, HA shows promise as a botanical insecticide for mosquito control.