New insecticide screening platforms indicate that Mitochondrial Complex I inhibitors are susceptible to cross-resistance by mosquito P450s that metabolise pyrethroids
| Autor: | Hanafy M. Ismail, Mark J. I. Paine, Rosemary Susan Lees, Adriana Adolfi, David Malone, Gareth J Lycett, Amalia Anthousi, Rhiannon A. E. Logan, Rachel Davies |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Piperonyl butoxide Multidisciplinary Pyrethroid biology Anopheles gambiae lcsh:R In vitro toxicology lcsh:Medicine 010501 environmental sciences biology.organism_classification 01 natural sciences Microbiology Genetically modified organism 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology chemistry In vivo parasitic diseases lcsh:Q Mode of action lcsh:Science Cross-resistance 0105 earth and related environmental sciences |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-10 (2020) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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