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Oruni, Ambrose, Lynd, Amy 
ORCID: https://orcid.org/0000-0001-6054-0525, Njoroge, Harun, Onyige, Ismail, Van 't Hof, Arjen, Matovu, Enock and Donnelly, Martin ORCID: https://orcid.org/0000-0001-5218-1497
(2024)
'Pyrethroid resistance and gene expression profile of a new resistant An. gambiae colony from Uganda reveals multiple resistance mechanisms and overexpression of Glutathione-S-Transferases linked to survival of PBO-pyrethroid combination'. Wellcome Open Research, Vol 9, e13.
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PMC11134160.pdf - Published Version Available under License Creative Commons Attribution. Download (1MB) | Preview |
Abstract
Background
The effectiveness of long-lasting insecticidal nets (LLINs) are being threatened by growing resistance to pyrethroids. To restore their efficacy, a synergist, piperonyl butoxide (PBO) which inhibits cytochrome P450s has been incorporated into pyrethroid treated nets. A trial of PBO-LLINs was conducted in Uganda from 2017 and we attempted to characterize mechanisms of resistance that could impact intervention efficacy.
Methods
We established an Anopheles gambiae s.s colony in 2018 using female mosquitoes collected from Busia district in eastern Uganda. We first assessed the phenotypic resistance profile of this colony using WHO tube and net assays using a deltamethrin dose-response approach. The Busia colony was screened for known resistance markers and RT-qPCR targeting 15 genes previously associated with insecticide resistance was performed.
Results
The Busia colony had very high resistance to deltamethrin, permethrin and DDT. In addition, the colony had moderate resistance to alpha-cypermethrin and lambda-cyhalothrin but were fully susceptible to bendiocarb and fenitrothion. Exposure to PBO in combination with permethrin and deltamethrin resulted in higher mortality rates in both net and tube assays, with a higher mortality observed in net assays than tube assays. The kdr marker, Vgsc-995S was at very high frequency (91.7-98.9%) whilst the metabolic markers Coeae1d and Cyp4j5-L43F were at very low (1.3% - 11.5%) and moderate (39.5% - 44.7%) frequencies respectively. Our analysis showed that gene expression pattern in mosquitoes exposed to deltamethrin, permethrin or DDT only were similar in comparison to the susceptible strain and there was significant overexpression of cytochrome P450s, glutathione-s-transferases (GSTs) and carboxyl esterases (COEs). However, mosquitoes exposed to both PBO and pyrethroid strikingly and significantly only overexpressed closely related GSTs compared to unexposed mosquitoes while major cytochrome P450s were underexpressed.
Conclusions
The high levels of pyrethroid resistance observed in Busia appears associated with a wide range of metabolic gene families.
| Item Type: | Article |
|---|---|
| Subjects: | QU Biochemistry > Genetics > QU 475 Genetic processes QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified. QX Parasitology > Insects. Other Parasites > QX 510 Mosquitoes 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) |
| Faculty: Department: | Biological Sciences > Vector Biology Department |
| Digital Object Identifer (DOI): | https://doi.org/10.12688/wellcomeopenres.19404.2 |
| SWORD Depositor: | JISC Pubrouter |
| Depositing User: | JISC Pubrouter |
| Date Deposited: | 18 Jun 2024 14:57 |
| Last Modified: | 18 Jun 2024 14:57 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/24717 |
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