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Cross-resistance profiles of malaria mosquito P450s associated with pyrethroid resistance against WHO insecticides

YuntaYanes, Cristina, Hemmings, Kay, Stevenson, Bradley, Koekemoer, Lizette L., Matambo, Tonderi, Pignatelli, Patricia, Voice, Michael, Nász, Szilárd and Paine, Mark ORCID: (2019) 'Cross-resistance profiles of malaria mosquito P450s associated with pyrethroid resistance against WHO insecticides'. Pesticide Biochemistry and Physiology, Vol 161, pp. 61-67.

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Extensive use of pyrethroids for malaria control in Africa has led to widespread pyrethroid resistance in the two major African vectors of malaria An. gambiae and An. funestus. This is often associated with constitutively elevated levels of cytochrome P450s involved with pyrethroid metabolism and detoxification. P450s have the capacity to metabolise diverse substrates, which raises concerns about their potential to cause cross-resistance. A bank of seven recombinant P450s from An. gambiae (CYPs 6M2, 6P2, 6P3, 6P4, 6P5, 9J5) and An. funestus (CYP6P9a) commonly associated with pyrethroid resistance were screened against twelve insecticides representing the five major classes of insecticides recommended by WHO for malaria control; permethrin, etofenprox and bifenthrin (type I pyrethroids), deltamethrin, lambda cyhalothrin and cypermethrin (type II pyrethroids), DDT (organochlorine), bendiocarb (carbamate), malathion, pirimiphos methyl and fenitrothion (organophosphates) and pyriproxyfen (juvenile hormone analogue). DDT was not metabolised by the P450 panel, while bendiocarb was only metabolised by CYP6P3. Pyrethroids and pyriproxyfen were largely susceptible to metabolism by the P450 panel, as were organophosphates, which are activated by P450s. Primiphos-methyl is increasingly used for malaria control. Examination of the pirimiphos-methyl metabolites generated by CYP6P3 revealed both the active pirimiphos-methyl-oxon form and the inactive oxidative cleavage product 2-diethylamino-6-hydroxy- 4-methylpyrimidine. The inhibition profile of CYPs 6M2, 6P2, 6P3, 6P9a and 9J5 was also examined using (DEF) as the probe substrate. Bendiocarb was the weakest inhibitor with IC⁠50>100μM across the P450 panel, while CYP6M2 showed strongest inhibition by malathion (IC⁠50 0.7μM). The results suggest that P450s present at elevated levels in two major Anopheline vectors of malaria in Africa have the capacity to metabolise a diverse range of pyrethroid and organophosphate insecticides as well as pyriproxyfen that could impact vector control.

Item Type: Article
Subjects: QX Parasitology > Insects. Other Parasites > QX 510 Mosquitoes
WA Public Health > Preventive Medicine > WA 240 Disinfection. Disinfestation. Pesticides (including diseases caused by)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department: Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):
Depositing User: Stacy Murtagh
Date Deposited: 23 Jul 2019 15:33
Last Modified: 13 Jun 2020 01:02


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