Identification and validation of a gene causing cross-resistance between insecticide classes in Anopheles gambiae from Ghana

Mitchell, Sara N., Stevenson, Bradley, Muller, Pie, Wilding, Craig, Egyir-Yawson, A., Field, S. G., Hemingway, Janet ORCID: https://orcid.org/0000-0002-3200-7173, Paine, M. J. I. ORCID: https://orcid.org/0000-0003-2061-7713, Ranson, Hilary ORCID: https://orcid.org/0000-0003-2332-8247 and Donnelly, M. J. ORCID: https://orcid.org/0000-0001-5218-1497 (2012) 'Identification and validation of a gene causing cross-resistance between insecticide classes in Anopheles gambiae from Ghana'. Proceedings of the National Academy of Sciences, Vol 109, Issue 16, pp. 6147-6152.

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Abstract

In the last decade there have been marked reductions in malaria incidence in sub-Saharan Africa. Sustaining these reductions will rely upon insecticides to control the mosquito malaria vectors. We report that in the primary African malaria vector, Anopheles gambiae sensu stricto, a single enzyme, CYP6M2, confers resistance to two classes of insecticide. This is unique evidence in a disease vector
of cross-resistance associated with a single metabolic gene that simultaneously reduces the efficacy of two of the four classes of insecticide routinely used for malaria control. The gene-expression profile of a highly DDT-resistant population of A. gambiae s.s. from Ghana was characterized using a uniquewhole-genome microarray. A number of genes were significantly overexpressed compared with two susceptible West African colonies, including genes from
metabolic families previously linked to insecticide resistance. One of the most significantly overexpressed probe groups (false-discovery rate-adjusted P < 0.0001) belonged to the cytochrome P450 gene CYP6M2. This gene is associated with pyrethroid resistance in wild A. gambiae s.s. populations) and can metabolize both type I and
type II pyrethroids in recombinant protein assays. Using in vitro assays we show that recombinant CYP6M2 is also capable of metabolizing the organochlorine insecticide DDT in the presence of solubilizing factor sodium cholate.

Item Type:	Article
Subjects:	QU Biochemistry > Genetics > QU 475 Genetic processes QX Parasitology > Insects. Other Parasites > QX 515 Anopheles QX Parasitology > Insects. Other Parasites > QX 600 Insect control. Tick control WA Public Health > Preventive Medicine > WA 240 Disinfection. Disinfestation. Pesticides (including diseases caused by) WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria WC Communicable Diseases > Tropical and Parasitic Diseases > WC 765 Prevention and control
Digital Object Identifer (DOI):	https://doi.org/10.1073/pnas.1203452109
Depositing User:	Users 183 not found.
Date Deposited:	19 Apr 2012 09:47
Last Modified:	17 Jul 2020 10:57
URI:	https://archive.lstmed.ac.uk/id/eprint/2833

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