Carbamate and pyrethroid resistance in the akron strain of Anopheles gambiae

Abstract

Insecticide resistance in the malaria vector, Anopheles gambiae is a serious problem, epitomized by the multi-resistant Akron strain, originally isolated in the country of Benin. Here we report resistance in this strain to pyrethroids and DDT (13-fold to 35-fold compared to the susceptible G3 strain), but surprisingly little resistance to etofenprox, a compound sometimes described as a “pseudo-pyrethroid.” There was also strong resistance to topically-applied commercial carbamates (45-fold to 81-fold), except for the oximes aldicarb and methomyl. Biochemical assays showed enhanced cytochrome P450 monooxygenase and carboxylesterase activity, but not that of glutathione-S-transferase. A series of substituted α,α,α,-trifluoroacetophenone oxime methylcarbamates were evaluated for enzyme inhibition potency and toxicity against G3 and Akron mosquitoes. The compound bearing an unsubstituted phenyl ring showed the greatest toxicity to mosquitoes of both strains. Low cross resistance in Akron was retained by all analogs in the series. Kinetic analysis of acetylcholinesterase activity and its inhibition by insecticides in the G3 strain showed inactivation rate constants greater than that of propoxur, and against Akron enzyme inactivation rate constants similar to that of aldicarb. However, inactivation rate constants against recombinant human AChE were essentially identical to that of the G3 strain. Thus, the acetophenone oxime carbamates described here, though potent insecticides that control resistant Akron mosquitoes, require further structural modification to attain acceptable selectivity and human safety.

An insecticide resistance-breaking mosquitocide targeting inward rectifier potassium channels in vectors of Zika virus and malaria

“…Furthermore, to ensure resistance, the mosquitoes from each resistant egg cohort were exposed to an LC99 dose (based on G3 toxicity values) of permethrin and propoxur. The mosquitoes used in this study were derived from the same colony that was used to demonstrate the resistance of the Akron strain to propoxur and permethrin that is attributed to both target site and metabolic resistance through upregulation of CYP450 enzymes21222349.…”

“…Mosquito strains not labeled by the same letter indicates statistical significance (P < 0.05) of the means as determined by a one-way ANOVA with Tukey’s post-hoc test. N.D. represents no data. 1 ED 50 , μg/mg (95% confidence limits). 2 RR: Resistance ratio for G3 = ED 50 Akron/ED 50 G3. * Topical ED 50 values from reference49.…”

Toxicity, mode of action, and synergist potential of flonicamid against mosquitoes

“…A C C E P T E D M A N U S C R I P T metabolic resistance factors present in this strain [28], an advantage for use in the field. It is interesting to note that feeding flonicamid or TFNA-AM at 1,000 ppm in sugar water did not result in significant mosquito mortality until 4 days of exposure, in contrast to the strong antifeedant properties associated with flonicamid in aphids [4,6].…”

Discovery of Species-selective and Resistance-breaking Anticholinesterase Insecticides for the Malaria Mosquito

“…Oxime carbamates derived from trifluoromethylketones have long been known to be insecticidal, [56] and thus a series of these compounds was investigated for their resistance-breaking activity and species-selectivity [57]. In particular, trifluoromethylketone oxime methylcarbamates 20 - 21 were found to rapidly inactivate both WT and G119S AgAChE, with SR values of 50–53.…”