{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:03:22Z","timestamp":1792706602135,"version":"4.5.0"},"reference-count":37,"publisher":"The Royal Society","issue":"1927","license":[{"start":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T00:00:00Z","timestamp":1590537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T00:00:00Z","timestamp":1590537600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Greek State Scholarships Foundation","award":["MIS-5000432"],"award-info":[{"award-number":["MIS-5000432"]}]},{"name":"Fondation Sante"},{"name":"EU Horizon 2020 Framework Program","award":["Superpests-688207"],"award-info":[{"award-number":["Superpests-688207"]}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Proc. R. Soc. B."],"published-print":{"date-parts":[[2020,5,27]]},"abstract":"<jats:p>\n            The putative synergistic action of target-site mutations and enhanced detoxification in pyrethroid resistance in insects has been hypothesized as a major evolutionary mechanism responsible for dramatic consequences in malaria incidence and crop production. Combining genetic transformation and CRISPR\/Cas9 genome modification, we generated transgenic\n            <jats:italic>Drosophila<\/jats:italic>\n            lines expressing pyrethroid metabolizing P450 enzymes in a genetic background along with engineered mutations in the voltage-gated sodium channel (\n            <jats:italic>para<\/jats:italic>\n            ) known to confer target-site resistance. Genotypes expressing the yellow fever mosquito\n            <jats:italic>Aedes aegypti Cyp9J28<\/jats:italic>\n            while also bearing the\n            <jats:italic>para<\/jats:italic>\n            <jats:sup>V1016G<\/jats:sup>\n            mutation displayed substantially greater resistance ratio (RR) against deltamethrin than the product of each individual mechanism (RR\n            <jats:sub>combined<\/jats:sub>\n            : 19.85 &gt; RR\n            <jats:sub>Cyp9J28<\/jats:sub>\n            : 1.77 \u00d7 RR\n            <jats:sub>V1016G<\/jats:sub>\n            : 3.00). Genotypes expressing\n            <jats:italic>Brassicogethes aeneus<\/jats:italic>\n            pollen beetle\n            <jats:italic>Cyp6BQ23<\/jats:italic>\n            and also bearing the\n            <jats:italic>para<\/jats:italic>\n            <jats:sup>L1014F<\/jats:sup>\n            (\n            <jats:italic>kdr<\/jats:italic>\n            ) mutation, displayed an almost multiplicative RR (RR\n            <jats:sub>combined<\/jats:sub>\n            : 75.19 \u2265 RR\n            <jats:sub>Cyp6BQ23<\/jats:sub>\n            : 5.74 \u00d7 RR\n            <jats:sub>L1014F<\/jats:sub>\n            : 12.74). Reduced pyrethroid affinity at the target site, delaying saturation while simultaneously extending the duration of P450-driven detoxification, is proposed as a possible underlying mechanism. Combinations of target site and P450 resistance loci might be unfavourable in field populations in the absence of insecticide selection, as they exert some fitness disadvantage in development time and fecundity. These are major considerations from the insecticide resistance management viewpoint in both public health and agriculture.\n          <\/jats:p>","DOI":"10.1098\/rspb.2020.0838","type":"journal-article","created":{"date-parts":[[2020,5,26]],"date-time":"2020-05-26T23:05:40Z","timestamp":1590534340000},"page":"20200838","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":55,"title":["\u2018What I cannot create, I do not understand\u2019: functionally validated synergism of metabolic and target site insecticide resistance"],"prefix":"10.1098","volume":"287","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8279-2114","authenticated-orcid":true,"given":"George-Rafael","family":"Samantsidis","sequence":"first","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, 100 N. Plastira Street, 70013 Heraklion, Crete, Greece"},{"name":"Department of Biology, University of Crete, Vassilika Vouton, 71409 Heraklion, Crete, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaela","family":"Panteleri","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, 100 N. Plastira Street, 70013 Heraklion, Crete, Greece"},{"name":"Department of Biology, University of Crete, Vassilika Vouton, 71409 Heraklion, Crete, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7291-1394","authenticated-orcid":true,"given":"Shane","family":"Denecke","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, 100 N. Plastira Street, 70013 Heraklion, Crete, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Kounadi","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, 100 N. Plastira Street, 70013 Heraklion, Crete, Greece"},{"name":"Department of Biology, University of Crete, Vassilika Vouton, 71409 Heraklion, Crete, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iason","family":"Christou","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, 100 N. Plastira Street, 70013 Heraklion, Crete, Greece"},{"name":"Department of Biology, University of Crete, Vassilika Vouton, 71409 Heraklion, Crete, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Nauen","sequence":"additional","affiliation":[{"name":"Bayer AG, CropScience Division, R&amp;D Pest Control, 40789 Monheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4608-7482","authenticated-orcid":true,"given":"Vassilis","family":"Douris","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, 100 N. Plastira Street, 70013 Heraklion, Crete, Greece"},{"name":"Department of Biological Applications and Technology, University of Ioannina, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8704-2574","authenticated-orcid":true,"given":"John","family":"Vontas","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, 100 N. Plastira Street, 70013 Heraklion, Crete, Greece"},{"name":"Laboratory of Pesticide Science, Department of Crop Science, Agricultural University of Athens, 118 55 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2020,5,27]]},"reference":[{"key":"e_1_3_6_2_2","unstructured":"WHO. 2018 WHO world malaria report 2018. 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