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To this regard, the molecular basis of permethrin, DDT and dieldrin resistance in<jats:italic>Anopheles funestus<\/jats:italic>(<jats:italic>sensu stricto<\/jats:italic>) at Akaka-Remo was investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Bioassays were conducted on 3\u20135-day-old adult<jats:italic>An. funestus<\/jats:italic>(<jats:italic>s.s.<\/jats:italic>) mosquitoes for permethrin, DDT and dieldrin susceptibility test. The molecular mechanisms of mosquito resistance to these insecticides were investigated using microarray and reverse transcriptase PCR techniques. The voltage-gated sodium channel region of mosquitoes was also screened for the presence of knockdown resistance mutations (<jats:italic>kdr<\/jats:italic>west and east) by sequencing method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Anopheles funestus<\/jats:italic>(<jats:italic>s.s.<\/jats:italic>) population was resistant to permethrin (mortality rate of 68%), DDT (mortality rate of 10%) and dieldrin (mortality rate of 8%) insecticides. Microarray and RT-PCR analyses revealed the overexpression of glutathione S-transferase genes, cytochrome P450s, esterase, trypsin and cuticle proteins in resistant mosquitoes compared to control. The<jats:italic>GSTe2<\/jats:italic>was the most upregulated detoxification gene in permethrin-resistant (FC\u2009=\u200944.89), DDT-resistant (FC\u2009=\u200957.39) and dieldrin-resistant (FC\u2009=\u200941.10) mosquitoes compared to control population (FC\u2009=\u200922.34). The cytochrome P450 gene,<jats:italic>CYP6P9b<\/jats:italic>was also upregulated in both permethrin- and DDT-resistant mosquitoes. The digestive enzyme, trypsin (hydrolytic processes) and the cuticle proteins (inducing cuticle thickening leading to reduced insecticides penetration) also showed high involvement in insecticide resistance, through their overexpression in resistant mosquitoes compared to control. The<jats:italic>kdr<\/jats:italic>east and west were absent in all mosquitoes analysed, suggesting their non-involvement in the observed mosquito resistance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The upregulation of metabolic genes, especially the<jats:italic>GSTe2<\/jats:italic>and trypsin, as well as the cuticle proteins is driving insecticide resistance of<jats:italic>An. funestus<\/jats:italic>(<jats:italic>s.s.<\/jats:italic>) population. However, additional molecular analyses, including functional metabolic assays of these genes as well as screening for a possible higher cuticular hydrocarbon and lipid contents, and increased procuticle thickness in resistant mosquitoes are needed to further describe their distinct roles in mosquito resistance.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13071-020-04296-8","type":"journal-article","created":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T12:03:21Z","timestamp":1597752201000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Investigating the molecular basis of multiple insecticide resistance in a major malaria vector Anopheles funestus (sensu stricto) from Akaka-Remo, Ogun State, Nigeria"],"prefix":"10.1186","volume":"13","author":[{"given":"Seun M.","family":"Atoyebi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevieve M.","family":"Tchigossou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romaric","family":"Akoton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob M.","family":"Riveron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Irving","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth","family":"Weedall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Tossou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Innocent","family":"Djegbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac O.","family":"Oyewole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adekunle A.","family":"Bakare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles S.","family":"Wondji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rousseau","family":"Djouaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,18]]},"reference":[{"key":"4296_CR1","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1186\/s12936-016-1615-9","volume":"15","author":"RJ Djouaka","year":"2016","unstructured":"Djouaka RJ, Atoyebi SM, Tchigossou GM, Riveron JM, Irving H, Akoton R, et al. 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