Substrate promiscuity of key resistance P450s confers clothianidin resistance while increasing chlorfenapyr potency in malaria vectors
Magellan Tchouakui,
Sulaiman S. Ibrahim,
Mersimine K. Mangoua,
Riccado F. Thiomela,
Tatiane Assatse,
Sonia L. Ngongang-Yipmo,
Abdullahi Muhammad,
Leon J.M. Mugenzi,
Benjamin D. Menze,
Themba Mzilahowa,
Charles S. Wondji
Affiliations
Magellan Tchouakui
Centre for Research in Infectious Diseases (CRID), Medical Entomology Department, P.O. Box 13501, Yaoundé, Cameroon; Corresponding author
Sulaiman S. Ibrahim
Centre for Research in Infectious Diseases (CRID), Medical Entomology Department, P.O. Box 13501, Yaoundé, Cameroon; Department of Biochemistry, Bayero University, PMB 3011, Kano, Nigeria; Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L35QA, UK
Mersimine K. Mangoua
Centre for Research in Infectious Diseases (CRID), Medical Entomology Department, P.O. Box 13501, Yaoundé, Cameroon
Riccado F. Thiomela
Centre for Research in Infectious Diseases (CRID), Medical Entomology Department, P.O. Box 13501, Yaoundé, Cameroon; Parasitology and Ecology Laboratory, Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon
Tatiane Assatse
Centre for Research in Infectious Diseases (CRID), Medical Entomology Department, P.O. Box 13501, Yaoundé, Cameroon; Parasitology and Ecology Laboratory, Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon
Sonia L. Ngongang-Yipmo
Centre for Research in Infectious Diseases (CRID), Medical Entomology Department, P.O. Box 13501, Yaoundé, Cameroon; Parasitology and Ecology Laboratory, Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon
Abdullahi Muhammad
Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L35QA, UK; Centre for Biotechnology Research, Bayero University, PMB 3011, Kano, Nigeria
Leon J.M. Mugenzi
Centre for Research in Infectious Diseases (CRID), Medical Entomology Department, P.O. Box 13501, Yaoundé, Cameroon
Benjamin D. Menze
Centre for Research in Infectious Diseases (CRID), Medical Entomology Department, P.O. Box 13501, Yaoundé, Cameroon
Themba Mzilahowa
Malaria Alert Centre (MAC), Kamuzu University of Health Sciences (KUHeS), Entomology Department, P.O. Box 265, Blantyre, Malawi
Charles S. Wondji
Centre for Research in Infectious Diseases (CRID), Medical Entomology Department, P.O. Box 13501, Yaoundé, Cameroon; Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L35QA, UK; International Institute of Tropical Agriculture (IITA), P.O. Box 2008, Yaoundé, Cameroon; Corresponding author
Summary: 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.
