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Ingham, Victoria 
ORCID: https://orcid.org/0000-0001-5708-4741, Pignatelli, Patricia, Moore, Jonathan D, Wagstaff, Simon ORCID: https://orcid.org/0000-0003-0577-5537 and Ranson, Hilary ORCID: https://orcid.org/0000-0003-2332-8247
(2017)
'The transcription factor Maf-S regulates metabolic resistance to insecticides in the malaria vector Anopheles gambiae.'. BMC Genomics, Vol 18, Issue 1, p. 669.
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Abstract
Malaria control in Africa is dependent upon the use insecticides but intensive use of a limited number of chemicals has led to resistance in mosquito populations. Increased production of enzymes that detoxify insecticides is one of the most potent resistance mechanisms. Several metabolic enzymes have been implicated in insecticide resistance but the processes controlling their expression have remained largely elusive. Here, we show that the transcription factor Maf-S regulates expression of multiple detoxification genes, including the key insecticide metabolisers CYP6M2 and GSTD1 in the African malaria vector Anopheles gambiae. Attenuation of this transcription factor through RNAi induced knockdown reduced transcript levels of these effectors and significantly increased mortality after exposure to the pyrethroid insecticides and DDT (permethrin: 9.2% to 19.2% (p = 0.015), deltamethrin: 3.9% to 21.6% (p = 0.036) and DDT: 1% to 11.7% (p = <0.01), whilst dramatically decreasing mortality induced by the organophosphate malathion (79.6% to 8.0% (p = <0.01)). Additional genes regulated by Maf-S were also identified providing new insight into the role of this transcription factor in insects. Maf-S is a key regulator of detoxification genes in Anopheles mosquitoes. Disrupting this transcription factor has opposing effects on the mosquito's response to different insecticide classes providing a mechanistic explanation to the negative cross resistance that has been reported between pyrethroids and organophosphates.
| Item Type: | Article |
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| Subjects: | QU Biochemistry > Proteins. Amino Acids. Peptides > QU 58.7 RNA QX Parasitology > Insects. Other Parasites > QX 510 Mosquitoes QX Parasitology > Insects. Other Parasites > QX 515 Anopheles WA Public Health > Preventive Medicine > WA 110 Prevention and control of communicable diseases. Transmission of infectious diseases 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 > Department of Tropical Disease Biology |
| Digital Object Identifer (DOI): | https://doi.org/10.1186/s12864-017-4086-7 |
| SWORD Depositor: | JISC Pubrouter |
| Depositing User: | Stacy Murtagh |
| Date Deposited: | 19 Sep 2017 14:51 |
| Last Modified: | 17 Sep 2019 13:33 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/7584 |
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