Functional genetic validation of key genes conferring insecticide resistance in the major African malaria vector, <i>Anopheles gambiae</i>

Adolfi, Adriana; Poulton, Beth C; Anthousi, Amalia; Macilwee, Stephanie L.; Ranson, Hilary; Lycett, Gareth

doi:10.1101/749457

Cited by 22 publications

(40 citation statements)

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“…In R. ferrugineus, the cytochrome P450 family is composed of 120 genes compared to 88 in D. melanogaster (http://flybase.org/). CYP6 and CYP12 (mitochondrial) are the most expanded gene families and R. ferrugineus has 104 CYP6 genes (and 16 CYP12), almost 5 times the 23 genes found in D. melanogaster, with a more specific expansion of subfamilies CYP6A (14 genes), CYP6G (9 genes) and CYP6D (5 genes), which have been associated with insecticide resistance 46,47 is even higher in H. hampei (116 CYP6 and 12 CYP12) and in D. ponderosae (117 CYP6 and 8 CYP12) showing that a dramatic expansion occurred in the Curculionidae in which it could mediate resistance to insecticide 33 . All pseudochromosomes, except #10, had genes for P450s.…”

Section: Tribolium Castaneummentioning

confidence: 99%

The genome of pest Rhynchophorus ferrugineus reveals gene families important at the plant-beetle interface

et al. 2020

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The red palm weevil, Rhynchophorus ferrugineus, infests palm plantations, leading to large financial losses and soil erosion. Pest-host interactions are poorly understood in R. ferrugineus, but the analysis of genetic diversity and pest origins will help advance efforts to eradicate this pest. We sequenced the genome of R. ferrugineus using a combination of paired-end Illumina sequencing (150 bp), Oxford Nanopore long reads, 10X Genomics and synteny analysis to produce an assembly with a scaffold N50 of~60 Mb. Structural variations showed duplication of detoxifying and insecticide resistance genes (e.g., glutathione S-transferase, P450, Rdl). Furthermore, the evolution of gene families identified those under positive selection including one glycosyl hydrolase (GH16) gene family, which appears to result from horizontal gene transfer. This genome will be a valuable resource to understand insect evolution and behavior and to allow the genetic modification of key genes that will help control this pest.

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Section: Tribolium Castaneummentioning

confidence: 99%

The genome of pest Rhynchophorus ferrugineus reveals gene families important at the plant-beetle interface

et al. 2020

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“…These were assayed against recently generated transgenic Gal4/UAS An. gambiae lines that overexpress the main P450s, CYP6P3 or CYP6M2 in multiple tissues, and demonstrate resistance to the pyrethroids, permethrin and deltamethrin in WHO bioassays 23 . These lines were assayed for sensitivity to fenpyroximate and tolfenpyrad in tarsal assays at fivefold concentration of LD95 in control mosquitoes obtained previously in Lees et al 2019 8 .…”

Section: Resultsmentioning

confidence: 99%

“…gambiae. These mosquitoes express the transgene P450s in a broad tissue pattern and at overall levels that are greater than wild type strains 23 . Although not necessarily at physiologically relevant levels, they provide a good indication that these P450s could confer cross-resistance to Complex I inhibitors in pyrethroid resistant wild strains that also express these enzymes at elevated levels.…”

Section: Discussionmentioning

confidence: 99%

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New insecticide screening platforms indicate that Mitochondrial Complex I inhibitors are susceptible to cross-resistance by mosquito P450s that metabolise pyrethroids

Lees

Ismail

Logan

et al. 2020

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Fenazaquin, pyridaben, tolfenpyrad and fenpyroximate are Complex I inhibitors offering a new mode of action for insecticidal malaria vector control. However, extended exposure to pyrethroid based products such as long-lasting insecticidal nets (LLINs) has created mosquito populations that are largely pyrethroid-resistant, often with elevated levels of P450s that can metabolise and neutralise diverse substrates. To assess cross-resistance liabilities of the Complex I inhibitors, we profiled their susceptibility to metabolism by P450s associated with pyrethroid resistance in Anopheles gambiae (CYPs 6M2, 6P3, 6P4, 6P5, 9J5, 9K1, 6Z2) and An. funestus (CYP6P9a). All compounds were highly susceptible. Transgenic An. gambiae overexpressing CYP6M2 or CYP6P3 showed reduced mortality when exposed to fenpyroximate and tolfenpyrad. Mortality from fenpyroximate was also reduced in pyrethroid-resistant strains of An. gambiae (VK7 2014 and Tiassalé 13) and An. funestus (FUMOZ-R). P450 inhibitor piperonyl butoxide (PBO) significantly enhanced the efficacy of fenpyroximate and tolfenpyrad, fully restoring mortality in fenpyroximate-exposed FUMOZ-R. Overall, results suggest that in vivo and in vitro assays are a useful guide in the development of new vector control products, and that the Complex I inhibitors tested are susceptible to metabolic cross-resistance and may lack efficacy in controlling pyrethroid resistant mosquitoes.

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“…These larvicides, upon application to breeding sites of mosquitoes, prevent their further development into adult forms, consequently, reducing adult mosquito population density and ultimately decreasing malaria transmission rates [16]. Meanwhile, the toxicity of many of the currently available insecticides to non-target species and the ever increasing resistance of Anopheles to commonly used classes of insecticides, necessitate the identification of novel targets for vector control [17][18][19][20][21]. Also, metabolic resistance to insecticides is mediated by the activities of detoxifying enzymes [22] and there is evidence that combining insecticides with the inhibitors of these enzymes can considerably reduce insecticide resistance [23].…”

Section: Introductionmentioning

confidence: 99%

Anopheles metabolic proteins in malaria transmission, prevention and control: a review

et al. 2020

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The increasing resistance to currently available insecticides in the malaria vector, Anopheles mosquitoes, hampers their use as an effective vector control strategy for the prevention of malaria transmission. Therefore, there is need for new insecticides and/or alternative vector control strategies, the development of which relies on the identification of possible targets in Anopheles. Some known and promising targets for the prevention or control of malaria transmission exist among Anopheles metabolic proteins. This review aims to elucidate the current and potential contribution of Anopheles metabolic proteins to malaria transmission and control. Highlighted are the roles of metabolic proteins as insecticide targets, in blood digestion and immune response as well as their contribution to insecticide resistance and Plasmodium parasite development. Furthermore, strategies by which these metabolic proteins can be utilized for vector control are described. Inhibitors of Anopheles metabolic proteins that are designed based on target specificity can yield insecticides with no significant toxicity to non-target species. These metabolic modulators combined with each other or with synergists, sterilants, and transmission-blocking agents in a single product, can yield potent malaria intervention strategies. These combinations can provide multiple means of controlling the vector. Also, they can help to slow down the development of insecticide resistance. Moreover, some metabolic proteins can be modulated for mosquito population replacement or suppression strategies, which will significantly help to curb malaria transmission.

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Functional genetic validation of key genes conferring insecticide resistance in the major African malaria vector, Anopheles gambiae

Abstract: 24 44(0)1517053137 25 Gareth.Lycett@lstmed.ac.uk 26

Cited by 22 publications

References 40 publications

The genome of pest Rhynchophorus ferrugineus reveals gene families important at the plant-beetle interface

The genome of pest Rhynchophorus ferrugineus reveals gene families important at the plant-beetle interface

New insecticide screening platforms indicate that Mitochondrial Complex I inhibitors are susceptible to cross-resistance by mosquito P450s that metabolise pyrethroids

Anopheles metabolic proteins in malaria transmission, prevention and control: a review

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