eprintid: 10188097 rev_number: 9 eprint_status: archive userid: 699 dir: disk0/10/18/80/97 datestamp: 2024-02-28 15:02:37 lastmod: 2024-02-28 15:02:37 status_changed: 2024-02-28 15:02:37 type: article metadata_visibility: show sword_depositor: 699 creators_name: Poulton, Beth C creators_name: Colman, Fraser creators_name: Anthousi, Amalia creators_name: Sattelle, David B creators_name: Lycett, Gareth J title: Aedes aegypti CCEae3A carboxylase expression confers carbamate, organophosphate and limited pyrethroid resistance in a model transgenic mosquito ispublished: inpress divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: K71 note: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ abstract: Insecticide resistance is a serious threat to our ability to control mosquito vectors which transmit pathogens including malaria parasites and arboviruses. Understanding the underlying mechanisms is an essential first step in tackling the challenges presented by resistance. This study aimed to functionally characterise the carboxylesterase, CCEae3A, the elevated expression of which has been implicated in temephos resistance in Aedes aegypti and Aedes albopictus larvae. Using our GAL4/UAS expression system, already established in insecticide-sensitive Anopheles gambiae mosquitoes, we produced transgenic An. gambiae mosquitoes that express an Ae. aegypti CCEae3A ubiquitously. This new transgenic line permits examination of CCEae3A expression in a background in which there is not a clear orthologue in Vectorbase and allows comparison with existing An. gambiae GAL4-UAS lines. Insecticide resistance profiling of these transgenic An. gambiae larvae indicated significant increases in resistance ratio for three organophosphate insecticides, temephos (6), chloropyriphos (6.6) and fenthion (3.2) when compared to the parental strain. Cross resistance to adulticides from three major insecticide classes: organophosphates (malathion, fenitrothion and pirimiphos methyl), carbamates (bendiocarb and propoxur) and pyrethroid (alpha-cypermethrin) was also detected. Resistance to certain organophosphates and carbamates validates conclusions drawn from previous expression and phenotypic data. However, detection of resistance to pirimiphos methyl and alphacypermethrin has not previously been formally associated with CCEae3A, despite occurring in Ae. aegypti strains where this gene was upregulated. Our findings highlight the importance of characterising individual resistance mechanisms, thereby ensuring accurate information is used to guide future vector control strategies. date: 2024-02-20 date_type: published publisher: Public Library of Science (PLoS) official_url: http://dx.doi.org/10.1371/journal.pntd.0011595 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2248764 doi: 10.1371/journal.pntd.0011595 medium: Print-Electronic pii: PNTD-D-23-01041 lyricists_name: Sattelle, David lyricists_id: DBSAT61 actors_name: Sattelle, David actors_id: DBSAT61 actors_role: owner full_text_status: public publication: PLOS Neglected Tropical Diseases volume: 18 number: 2 article_number: e0011595 event_location: United States editors_name: Acosta-Serrano, Álvaro citation: Poulton, Beth C; Colman, Fraser; Anthousi, Amalia; Sattelle, David B; Lycett, Gareth J; (2024) Aedes aegypti CCEae3A carboxylase expression confers carbamate, organophosphate and limited pyrethroid resistance in a model transgenic mosquito. PLOS Neglected Tropical Diseases , 18 (2) , Article e0011595. 10.1371/journal.pntd.0011595 <https://doi.org/10.1371/journal.pntd.0011595>. (In press). Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10188097/1/Sattelle_Poulton%20et%20al%202023%20-%20Revised%20manuscript%20%28clean%20copy_figs%29.pdf