diethyl-maleate and butyl-phosphorotrithioate

Aedes aegypti (L.) is the primary vector of Zika, dengue, yellow fever, and chikungunya viruses. Insecticides used in mosquito control can help prevent the spread of vector-borne diseases. However, it is essential to determine insecticide resistance (IR) status before control measures are undertaken. Only the most effective insecticides should be used to avoid ineffective control and/or promotion of IR. Pyrethroids and organophosphates are the most commonly used insecticides for mosquito control. Here, the efficacy of two active ingredients (AIs; permethrin [pyrethroid], chlorpyrifos [organophosphate]), two formulated products (FPs; Biomist [AI: permethrin]) and (Mosquitomist [AI: chlorpyrifos]), and three synergists (piperonyl butoxide, diethyl maleate, S-S-S-tributyl phosphorotrithioate) was evaluated in two Ae. aegypti colonies (pyrethroid resistant and susceptible). Mosquitomist was most effective against the pyrethroid-resistant colony (100% mortality at diagnostic time). Pre-exposure to synergists did not increase the efficacy of AIs against the pyrethroid-resistant colony. Further research is needed to discover how synergists may affect the efficacy of insecticides when used on pyrethroid-resistant mosquitoes.

Topics: Aedes; Animals; Chlorpyrifos; Female; Insecticide Resistance; Insecticides; Longevity; Maleates; Organothiophosphates; Permethrin; Pesticide Synergists; Piperonyl Butoxide

Synergists can counteract metabolic insecticide resistance by inhibiting detoxification enzymes or transporters. They are used in commercial formulations of insecticides, but are also frequently used in the elucidation of resistance mechanisms. However, the effect of synergists on genome-wide transcription in arthropods is poorly understood. In this study we used Illumina RNA-sequencing to investigate genome-wide transcriptional responses in an acaricide resistant strain of the spider mite Tetranychus urticae upon exposure to synergists such as S,S,S-tributyl phosphorotrithioate (DEF), diethyl maleate (DEM), piperonyl butoxide (PBO) and cyclosporin A (CsA). Exposure to PBO and DEF resulted in a broad transcriptional response and about one third of the differentially expressed genes (DEGs), including cytochrome P450 monooxygenases and UDP-glycosyltransferases, was shared between both treatments, suggesting common transcriptional regulation. Moreover, both DEF and PBO induced genes that are strongly implicated in acaricide resistance in the respective strain. In contrast, CsA treatment mainly resulted in downregulation of Major Facilitator Superfamily (MFS) genes, while DEGs of the DEM treatment were not significantly enriched for any GO-terms.

Topics: Acaridae; Animals; Cyclosporine; Genome, Insect; Insecticide Resistance; Insecticides; Maleates; Organothiophosphates; Pesticide Synergists; Piperonyl Butoxide; Transcriptome

Phytoseiulus macropilis Banks (Acari: Phytoseiidae) is an effective predator of Tetranychus urticae Koch (Acari: Tetranychidae). The objectives of this research were to study the stability of fenpropathrin resistance and the cross-resistance relationships with different pyrethroids, and also to evaluate the effect of synergists [piperonyl butoxide (PBO), diethyl maleate (DEM) and S,S,S-tributyl phosphorotrithioate (DEF)] on fenpropathrin resistant and susceptible strains of this predaceous mite. The stability of fenpropathrin resistance was studied under laboratory conditions, using P. macropilis populations with initial frequencies of 75 and 50% of resistant mites. The percentages of fenpropathrin resistant mites were evaluated monthly for a period of up to 12 months. A trend toward decreased resistance frequencies was observed only during the first 3-4 months. After this initial decrease, the fenpropathrin resistance was shown to be stable, maintaining constant resistance frequencies (around 30%) until the end of the evaluation period. Toxicity tests carried out using fenpropathrin resistant and susceptible strains of P. macropilis indicated strong positive cross-resistance between fenpropathrin and the pyrethroids bifenthrin and deltamethrin. Bioassays with the synergists DEM, DEF and PBO were also performed. The maximum synergism ratio (SR = LC50 without synergist/LC50 with synergist) detected for the three evaluated synergists (PBO, DEM, DEF) was 5.86 (for DEF), indicating low influence of enzyme detoxification processes in fenpropathrin resistance.

Topics: Acaricides; Animals; Drug Resistance; Drug Synergism; Maleates; Mites; Nitriles; Organothiophosphates; Piperonyl Butoxide; Pyrethrins

The Asiatice stem borer, Chilo suppressalis (Walker), an important rice insect pest in China, has developed resistances to several classes of insecticides. To control C. suppressalis, chlorantraniliprole has been introduced as a novel insecticide in rice field since 2008. It is an anthranilic diamide insecticide that binds and activates ryanodine receptors (RyR). The susceptibility of field populations of C. suppressalis to chlorantraniliprole was determined in this study. The hypotheses of equality and parallelism showed that regression lines in the tested five populations were neither equal nor parallel. The Ruian, Cangnan, and Liangyungang populations (RA12, CN12, and LYG12) collected in 2012 had lower LD50 values, whereas the Zhuji populations (ZJ12 and ZJ13) collected in 2012 and 2013 were approximately 15 times more tolerant than the RA12 population. To determine the potential mechanisms involved in this tolerance variation, synergism bioassays were performed. Significant differences in susceptibility were found between without synergist and with synergist for the three populations (RA12, LYG12, and ZJ13), based on the tests for the hypotheses of equality. In RA12 and LYG12 populations with chlorantraniliprole, the addition of piperonyl butoxide (PBO) significantly synergized the activity, with synergism ratios of 2.68- and 2.33-fold, respectively, whereas addition of S,S,S-tributyl phosphorotrithioate (DEF) and diethyl maleate (DEM) had no synergist effect. In ZJ13 population with chlorantraniliprole, the addition of PBO and DEF increased synergism ratios by 12.43- and 6.31-fold, respectively, whereas addition of DEM had no significant effect on the toxicity against ZJ13 larvae. These susceptibility and synergism data suggested that detoxification enzymes might be involved in the tolerance variation to chlorantraniliprole in field populations of C. suppressalis.

Topics: Animals; China; Insecticide Resistance; Insecticides; Larva; Maleates; Moths; Organothiophosphates; ortho-Aminobenzoates; Pesticide Synergists; Piperonyl Butoxide; Seasons

Spinosad, a relatively new, effective and safe pesticide, has been widely used in pest control over the last 10 years. However, different levels of resistance to this insecticide have developed in some insects worldwide.. After continuous selection for 27 generations, a strain (SpRR) of the housefly developed 247-fold resistance to spinosad compared with the laboratory susceptible strain (CSS). The estimated realised heritability (h(2) ) of spinosad resistance was 0.14. There was no significant difference in the LD(50) values and slopes between reciprocal progenies F(1) and F(1) ', and values of 0.33 (F(1) ) and 0.30 (F(1) ') were obtained for the degree of dominance. Chi-square analysis from responses of self-bred (F(2) ) and backcrosses (BC(1) and BC(2) ) were highly significant, suggesting that the resistance was probably controlled by more than one gene. Synergists piperonyl butoxide (PBO), diethyl maleate (DEM) and S,S,S-tributyl phosphorotrithioate (DEF) affected the toxicity of spinosad at a low level, and demonstrated that metabolic-mediated detoxification was not an important factor in conferring resistance to spinosad in the SpRR strain.. It was concluded that spinosad resistance in the housefly was autosomal and incompletely dominant, and the resistance was probably controlled by more than one gene. These results provide the basic information for designing successful management programmes for the control of houseflies.

Topics: Animals; Crosses, Genetic; Drug Combinations; Female; Houseflies; Insecticide Resistance; Insecticides; Lethal Dose 50; Macrolides; Male; Maleates; Organothiophosphates; Piperonyl Butoxide

Permethrin is the active component of topical creams widely used to treat human scabies. Recent evidence has demonstrated that scabies mites are becoming increasingly tolerant to topical permethrin and oral ivermectin. An effective approach to manage pesticide resistance is the addition of synergists to counteract metabolic resistance. Synergists are also useful for laboratory investigation of resistance mechanisms through their ability to inhibit specific metabolic pathways.. To determine the role of metabolic degradation as a mechanism for acaricide resistance in scabies mites, PBO (piperonyl butoxide), DEF (S,S,S-tributyl phosphorotrithioate) and DEM (diethyl maleate) were first tested for synergistic activity with permethrin in a bioassay of mite killing. Then, to investigate the relative role of specific metabolic pathways inhibited by these synergists, enzyme assays were developed to measure esterase, glutathione S-transferase (GST) and cytochrome P450 monooxygenase (cytochrome P450) activity in mite extracts. A statistically significant difference in median survival time of permethrin-resistant Sarcoptes scabiei variety canis was noted when any of the three synergists were used in combination with permethrin compared to median survival time of mites exposed to permethrin alone (p<0.0001). Incubation of mite homogenates with DEF showed inhibition of esterase activity (37%); inhibition of GST activity (73%) with DEM and inhibition of cytochrome P450 monooxygenase activity (81%) with PBO. A 7-fold increase in esterase activity, a 4-fold increase in GST activity and a 2-fold increase in cytochrome P450 monooxygenase activity were observed in resistant mites compared to sensitive mites.. These findings indicate the potential utility of synergists in reversing resistance to pyrethroid-based acaricides and suggest a significant role of metabolic mechanisms in mediating pyrethroid resistance in scabies mites.

Topics: Acaricides; Animals; Cytochrome P-450 Enzyme System; Drug Resistance; Enzyme Inhibitors; Esterases; Glutathione Transferase; Insecticides; Maleates; Organothiophosphates; Permethrin; Pesticide Synergists; Piperonyl Butoxide; Pyrethrins; Sarcoptes scabiei; Scabies

Two mosquito strains of Culex quinquefasciatus Say, MAmCq and HAmCq, were collected from Mobile and Huntsville, AL, respectively, after the control of mosquitoes with insecticides proved difficult. A synergism study showed that resistance to chlorpyrifos in MAmCq and HAmCq was not suppressed by piperonyl butoxide (PBO) and S,S,S,-tributylphosphorotrithioate (DEF), suggesting that P450 monooxygenase- and hydrolase-mediated detoxication does not contribute to chlorpyrifos resistance in either strain. Diethyl maleate (DEM) did not cause any significant change in the level of chlorpyrifos toxicity to HAmCq. However, DEM enhanced toxicity of chlorpyrifos to MAmCq 2.5-fold, indicating that glutathione S-transferase (GST)-mediated detoxication may play a minor role in the resistance of MAmCq. An inhibition study of acetylcholinesterase (AChE) by chlorpyrifos showed that bimolecular rate constants (Ki) of chlorpyrifos for the inhibition of AChE in adults and larvae of the susceptible S-Lab strain were 2.2- and 1.9-fold higher, respectively, than in the HAmCq strain and 3.4- and 3.8-fold higher than in the MAmCq strain. The single mutation, G119S, resulting from a single nucleotide polymorphism (SNP), G to A, in ace-1 acetylcholinesterase gene was present in HAmCq and MAmCq mosquitoes. The frequency of the heterozygote for the G119S mutant allele in the HAmCq and MAmCq mosquito populations was 0.25 and 0.45, respectively, and no individuals in either of these mosquito strains were homozygous for the A allele. It thus seems likely that the presence of heterozygous individuals for the G119S allele in HAmCq and MAmCq populations may be a response to the insensitivity of AChE observed in these two mosquito strains.

Topics: Acetylcholinesterase; Alabama; Animals; Base Sequence; Chlorpyrifos; Cholinesterase Inhibitors; Culex; DNA Primers; Dose-Response Relationship, Drug; Heterozygote; Insecticide Resistance; Insecticides; Maleates; Organothiophosphates; Piperonyl Butoxide; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Species Specificity