Select plant alkaloids synergize the toxicity and neural block of natural pyrethrins in Aedes aegypti

Authors: Norris, Edmund; BLOOMQUIST, JEFFREY - University Of Florida

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 1/27/2021
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: With ever growing numbers of mosquito populations becoming resistant to a wide variety of insecticides, new insecticidal technologies are needed. However, the lack of new insecticidal chemical classes to control mosquito populations presents a significant hurdle in the continual control of mosquito populations. As such, the development of novel synergists may be a viable alternative approach. We explored the potential of two plant-derived, sodium channel-directed alkaloids, veratrine and aconitine, as both insecticides and synergists of natural pyrethrins (NP) on Aedes aegypti adults and larvae. Aconitine was more toxic than veratrine, with an LD50 of 165 ng/mg compared to 300 ng/mg on the pyrethroid-susceptible Orlando strain, but significant resistance was observed for aconitine on the pyrethroid-resistant Puerto Rico strain (RR = 14.5). When applied in mixtures with piperonyl butoxide (PBO) and natural pyrethrins, large synergism values were obtained. Aconitine + PBO synergized natural pyrethrins 21.8-fold, whereas veratrine + PBO synergized natural pyrethrins 5.3-fold on the Orlando strain. Less synergism of natural pyrethrins was observed on the resistant Puerto Rico strain, with acontine + PBO synergizing natural pyrethrins only 4.1-fold and veratrine + PBO synergizing natural pyrethrins 9.5-fold. When alkaloids were applied alone on the mosquito larval central nervous system (CNS), aconitine was less active on the pyrethroid-resistant strain (block at 10 µM) than on the pyrethroid-susceptible strain (block at 100 µM). However, the opposite was true for veratrine, as the pyrethroid-resistant CNS was at least three times more sensitive to this compound. The nerve blocking effect of NP was significantly synergized by both compounds on the pyrethroid-susceptible strain (approximately 10-fold synergism), however only veratrine synergized NP block on the pyrethroid-susceptible strain (10-fold synergism). These results demonstrate that pyrethroid-resistance in the Puerto Rico strain also produces resistance to aconitine, presumably by altering aconitine binding at the sodium channel. These results highlight the potential of site II sodium channel activators to synergize natural pyrethroids and may represent future additives to insecticide formulations. Moreover, differences in the ability of each compound to synergize NP on the pyrethroid-susceptible and pyrethroid-resistant strains may highlight physicochemical properties that are necessary for synergizing natural pyrethrins at pyrethroid-insensitive sodium channels.