Pyriproxyfen is metabolized by P450s associated with pyrethroid resistance in An. gambiae.
Pyrethroid resistance is widespread in the malaria vector Anopheles gambiae leading to concerns about the future efficacy of bednets with pyrethroids as the sole active ingredient. The incorporation of pyriproxyfen (PPF), a juvenile hormone analogue, into pyrethroid treated bednets is being trialed in Africa. Pyrethroid resistance is commonly associated with elevated levels of P450 expression including CYPs 6M2, 6P2, 6P3, 6P4, 6P5, 6Z2 and 9J5. Having expressed these P450s in E. coli we find all are capable of metabolizing PPF. Inhibition of these P450s by permethrin, deltamethrin and PPF was also examined. Deltamethrin and permethrin were moderate inhibitors (IC501-10 μM) of diethoxyfluorescein (DEF) activity for all P450s apart from CYP6Z2 (IC50> 10 μM), while PPF displayed weaker inhibition of all P450s (IC50> 10 μM) except CYP's 6Z2 and 6P2 (IC501-10 μM). We found evidence of low levels of cross resistance between PPF and other insecticide classes by comparing the efficacy of PPF in inhibiting metamorphosis and inducing female sterility in an insecticide susceptible strain of An. gambiae and a multiple resistant strain from Cote d'Ivoire.
Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK.
Cristina
C
Yunta
Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK.
Nelson
N
Grisales
Syngenta, Product Metabolism and Analytical Sciences, Jealott's Hill International Research Centre, Bracknell, RG42 6EY, UK.
Szilárd
S
Nász
Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK.
Kay
K
Hemmings
Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK.
Patricia
P
Pignatelli
Cypex Ltd, Tom McDonald Avenue, Dundee, DD2 1NH, UK.
Michael
M
Voice
Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK.
Hilary
H
Ranson
Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK. Electronic address: mark.paine@lstmed.ac.uk.
Mark J I
MJ
Paine
D000818:Animals; D000852:Anopheles / Q000187:drug effects* / Q000502:physiology*; D007560:Cote d'Ivoire; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics*; D005260:Female; D019476:Insect Proteins / Q000378:metabolism*; D007305:Insecticide Resistance; D007306:Insecticides / Q000494:pharmacology*; D008675:Metamorphosis, Biological; D030781:Organisms, Genetically Modified; D011725:Pyridines / Q000494:pharmacology*; D012098:Reproduction
D019476:Insect Proteins; D007306:Insecticides; D011725:Pyridines; C055613:pyriproxyfen; D003577:Cytochrome P-450 Enzyme System
Insecticide resistance; Olyset Duo; P450; Pyriproxyfen