Pyriproxyfen is metabolized by P450s associated with pyrethroid resistance in An. gambiae.

Pyriproxyfen is metabolized by P450s associated with pyrethroid resistance in An. gambiae.
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羟基芬芬被An中的P450代谢。冈比亚。

DOI:
10.1016/j.ibmb.2016.09.001
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发表时间:
2016-11
影响因子:
3.8
通讯作者:
Paine MJ
Paine MJ
中科院分区:
农林科学2区
文献类型:
--
作者:
Yunta C;Grisales N;Nász S;Hemmings K;Pignatelli P;Voice M;Ranson H;Paine MJ

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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 (IC50 1–10 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 (IC50 1–10 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. Pyriproxyfen is metabolized by P450s associated with pyrethroid resistance. Pyrethroids may synergise pyriproxyfen activity. Pyriproxyfen efficacy is compromised in a multiple resistant An. gambiae strain. Resistance monitoring for pyriproxyfen chemistry is recommended.
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