Substrate promiscuity of key resistance P450s confers clothianidin resistance while increasing chlorfenapyr potency in malaria vectors.

Tchouakui, Magellan, Ibrahim, SulaimanSadi, Mangoua, Mersimine K, Thiomela, Riccado F, Assatse, Tatiane, Ngongang-Yipmo, Sonia L, Muhammad, Abdullahi, Mugenzi, Leon J M, Menze, Benjamin D, Mzilahowa, Themba and Wondji, Charles ORCID: https://orcid.org/0000-0003-0791-3673 (2024) 'Substrate promiscuity of key resistance P450s confers clothianidin resistance while increasing chlorfenapyr potency in malaria vectors.'. Cell reports, Vol 43, Issue 8, p. 114566.

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Abstract

Novel insecticides were recently introduced to counter pyrethroid resistance threats in African malaria vectors. To prolong their effectiveness, potential cross-resistance from promiscuous pyrethroid metabolic resistance mechanisms must be elucidated. Here, we demonstrate that the duplicated P450s CYP6P9a/-b, proficient pyrethroid metabolizers, reduce neonicotinoid efficacy in Anopheles funestus while enhancing the potency of chlorfenapyr. Transgenic expression of CYP6P9a/-b in Drosophila confirmed that flies expressing both genes were significantly more resistant to neonicotinoids than controls, whereas the contrasting pattern was observed for chlorfenapyr. This result was also confirmed by RNAi knockdown experiments. In vitro expression of recombinant CYP6P9a and metabolism assays established that it significantly depletes both clothianidin and chlorfenapyr, with metabolism of chlorfenapyr producing the insecticidally active intermediate metabolite tralopyril. This study highlights the risk of cross-resistance between pyrethroid and neonicotinoid and reveals that chlorfenapyr-based control interventions such as Interceptor G2 could remain efficient against some P450-based resistant mosquitoes.

Item Type:	Article
Subjects:	WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department:	Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.1016/j.celrep.2024.114566
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	06 Sep 2024 10:22
Last Modified:	06 Sep 2024 10:22
URI:	https://archive.lstmed.ac.uk/id/eprint/25160

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