Dataset Information

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

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.

SUBMITTER: Tchouakui M

PROVIDER: S-EPMC11372441 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Tchouakui Magellan M Ibrahim Sulaiman S SS Mangoua Mersimine K MK Thiomela Riccado F RF Assatse Tatiane T Ngongang-Yipmo Sonia L SL Muhammad Abdullahi A Mugenzi Leon J M LJM Menze Benjamin D BD Mzilahowa Themba T Wondji Charles S CS

Cell reports 20240731 8

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 confir ...[more]

PMID: 39088320

Similar Datasets

Project description:BackgroundMalaria vector control is dependent on chemical insecticides applied to walls by indoor residual spraying or on long-lasting insecticidal nets. The emergence and spread of insecticide resistance in major malaria vectors may compromise malaria control and elimination efforts. The aim of this study was to estimate a diagnostic dose for chlorfenapyr (class: pyrrole) and clothianidin (class: neonicotinoid) and assess the baseline susceptibility of three major Anopheles malaria vectors of western Kenya to these two insecticides.MethodsThe Centers for Disease Control and Prevention (CDC) bottle assay was used to determine the diagnostic doses of chlorfenapyr and clothianidin insecticides against the susceptible Kisumu strain of Anopheles gambiae. Probit analysis was used to determine the lethal doses at which 50% (LD50) and 99% (LD99) of the susceptible mosquitoes would be killed 24, 48 and 72 h following exposure for 1 h. Insecticidal efficacy of chlorfenapyr, clothianidin and the pyrethroid deltamethrin was then evaluated against field collected female Anopheles mosquitoes sampled from Nyando, Bumula and Ndhiwa sub-Counties in western Kenya. Members of Anopheles funestus and An. gambiae complexes were identified using polymerase chain reaction (PCR).ResultsThe determined diagnostic doses of chlorfenapyr and clothianidin insecticides were 50 µg/bottle and 150 µg/bottle, respectively, for An. gambiae, Kisumu strain. When exposed to the diagnostic dose of each insecticide, Anopheles malaria vector populations in western Kenya were susceptible to both insecticides with 100% mortality observed after 72 h. Mortality of mosquitoes exposed to deltamethrin increased over time but did not reach 100%. Mortality of Anopheles arabiensis from Nyando exposed to deltamethrin was 83% at 24 h, 88% at 48 h and 94.5% at 72 h while An. funestus from Ndhiwa was 89% at 24 h, 91.5% at 48 h and 94.5% at 72 h.ConclusionMosquitoes of western Kenya, despite being resistant to pyrethroids, are susceptible to chlorfenapyr and clothianidin. Field evaluations of the formulated product are needed.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets