{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:47:05Z","timestamp":1790790425926,"version":"4.1.0"},"reference-count":52,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"3","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,1]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n<jats:p>The extensive use of chemical insecticides for public health and agricultural purposes has increased the occurrence and development of insecticide resistance. This study used transcriptome sequencing to screen 10 upregulated metabolic detoxification enzyme genes from <jats:italic>Aedes albopictus<\/jats:italic> resistant strains. Of these, <jats:italic>CYP6A14<\/jats:italic> and <jats:italic>CYP6N6<\/jats:italic> were found to be substantially overexpressed in the deltamethrin-induced expression test, indicating their role in deltamethrin resistance in <jats:italic>Ae. albopictus<\/jats:italic>. Furthermore, the corresponding 60-kDa recombinant proteins, CYP6A14 and CYP6N6, were successfully expressed using the <jats:italic>Escherichia coli<\/jats:italic> expression system. Enzyme activity studies revealed that <jats:italic>CYP6A14<\/jats:italic> (5.84 U\/L) and <jats:italic>CYP6N6<\/jats:italic> (6.3 U\/L) have cytochrome P450 (CYP450) enzyme activity. In vitro, the metabolic analysis revealed that the recombinant proteins degraded deltamethrin into 1-oleoyl-sn-glycero-3-phosphoethanolamine and 2\u2032,2\u2032-dibromo-2\u2032-deoxyguanosine. Subsequently, the CYP450 genes in larvae of <jats:italic>Ae. albopictus<\/jats:italic> were silenced by RNA interference technology to study deltamethrin resistance in\u00a0vivo. The silencing of <jats:italic>CYP6A14<\/jats:italic> and <jats:italic>CYP6N6<\/jats:italic> increased the mortality rate of mosquitoes without affecting their survival time, spawning quantity, hatching rate, and other normal life activities. Altogether, <jats:italic>CYP6A14<\/jats:italic> and <jats:italic>CYP6N6<\/jats:italic> belong to the <jats:italic>CYP6<\/jats:italic> family and mutually increase deltamethrin resistance in <jats:italic>Ae. albopictus<\/jats:italic>.<\/jats:p>","DOI":"10.4269\/ajtmh.22-0524","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T15:35:43Z","timestamp":1675697743000},"page":"609-618","source":"Crossref","is-referenced-by-count":7,"title":["In\u00a0Vitro and In\u00a0Vivo Validation of CYP6A14 and CYP6N6 Participation in Deltamethrin Metabolic Resistance in Aedes albopictus"],"prefix":"10.4269","volume":"108","author":[{"given":"Hui","family":"Peng","sequence":"first","affiliation":[{"name":"Shandong Institute of Parasitic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jining, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Institute of Parasitic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jining, China;"},{"name":"Department of Laboratory Medicine, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuxia","family":"Guo","sequence":"additional","affiliation":[{"name":"Shandong Institute of Parasitic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jining, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxiang","family":"Lv","sequence":"additional","affiliation":[{"name":"Shandong Institute of Parasitic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jining, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Shandong Institute of Parasitic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jining, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifang","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Institute of Parasitic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jining, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Shandong Institute of Parasitic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jining, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Liu","sequence":"additional","affiliation":[{"name":"Shandong Institute of Parasitic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jining, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maoqing","family":"Gong","sequence":"additional","affiliation":[{"name":"Shandong Institute of Parasitic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jining, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"b1","series-title":"Nature","first-page":"504","article-title":"The global distribution and burden of dengue","volume":"496","author":"Bhatt","year":"2013"},{"key":"b2","series-title":"PLoS Med","first-page":"e1001619","article-title":"The impact of pyrethroid resistance on the efficacy of insecticide-treated bed nets against African anopheline mosquitoes: systematic review and meta-analysis","volume":"11","author":"Strode","year":"2014"},{"key":"b3","series-title":"Nature","first-page":"207","article-title":"The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015","volume":"526","author":"Bhatt","year":"2015"},{"key":"b4","series-title":"Malar J","first-page":"235","article-title":"Therapeutic efficacy of artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Mali, 2015\u20132016","volume":"20","author":"Diarra","year":"2021"},{"key":"b5","series-title":"Pestic Biochem Physiol","first-page":"61","article-title":"Cross-resistance profiles of malaria mosquito P450s associated with pyrethroid resistance against WHO insecticides","volume":"161","author":"Yunta","year":"2019"},{"key":"b6","series-title":"PLoS One","first-page":"e95640","article-title":"Negative cross resistance mediated by co-treated bed nets: a potential means of restoring pyrethroid-susceptibility to malaria vectors","volume":"9","author":"White","year":"2014"},{"key":"b7","series-title":"Pestic Biochem Physiol","first-page":"104666","article-title":"Cytochrome P450-based metabolic insecticide resistance in Anopheles and Aedes mosquito vectors: muddying the waters","volume":"170","author":"Vontas","year":"2020"},{"key":"b8","series-title":"Nature","first-page":"376","article-title":"A sensory appendage protein protects malaria vectors from pyrethroids","volume":"577","author":"Ingham","year":"2020"},{"key":"b9","series-title":"Proc Biol Sci","first-page":"20191091","article-title":"Mosquitoes cloak their legs to resist insecticides","volume":"286","author":"Balabanidou","year":"2019"},{"key":"b10","series-title":"Malar J","first-page":"156","article-title":"Insecticide resistance patterns in Uganda and the effect of indoor residual spraying with bendiocarb on kdr L1014S frequencies in Anopheles gambiae s.s","volume":"16","author":"Abeku","year":"2017"},{"key":"b11","series-title":"Front Microbiol","first-page":"870462","article-title":"Role of insect gut microbiota in pesticide degradation: a review","volume":"13","author":"Siddiqui","year":"2022"},{"key":"b12","series-title":"PLoS Genet","first-page":"e1004236","article-title":"CYP6 P450 enzymes and ACE-1 duplication produce extreme and multiple insecticide resistance in the malaria mosquito Anopheles gambiae","volume":"10","author":"Edi","year":"2014"},{"key":"b13","series-title":"Philos Trans R Soc Lond B Biol Sci","first-page":"20120429","article-title":"Role of cytochrome P450s in insecticide resistance: impact on the control of mosquito-borne diseases and use of insecticides on Earth","volume":"368","author":"David","year":"2013"},{"key":"b14","series-title":"PLoS One","first-page":"e0130719","article-title":"The impact of selection with diflubenzuron, a chitin synthesis inhibitor, on the fitness of two Brazilian Aedes aegypti field populations","volume":"10","author":"Belinato","year":"2015"},{"key":"b15","series-title":"Insects","first-page":"276","article-title":"From global to local-new insights into features of pyrethroid detoxification in vector mosquitoes","volume":"12","author":"Black","year":"2021"},{"key":"b16","series-title":"Insect Mol Biol","first-page":"3","article-title":"Insect glutathione transferases and insecticide resistance","volume":"14","author":"Enayati","year":"2005"},{"key":"b17","series-title":"PLoS Negl Trop Dis","first-page":"e0006828","article-title":"Comparative transcriptome analysis and RNA interference reveal CYP6A8 and SNPs related to pyrethroid resistance in Aedes albopictus.","volume":"12","author":"Xu","year":"2018"},{"key":"b18","series-title":"Int J Mol Sci","first-page":"1409","article-title":"ATP-binding cassette (ABC) transporter genes involved in pyrethroid resistance in the malaria vector Anopheles sinensis: genome-wide identification, characteristics, phylogenetics, and expression profile","volume":"20","author":"He","year":"2019"},{"key":"b19","series-title":"Malar J","first-page":"62","article-title":"UDP-glycosyltransferase genes and their association and mutations associated with pyrethroid resistance in Anopheles sinensis (Diptera: Culicidae)","volume":"18","author":"Zhou","year":"2019"},{"key":"b20","series-title":"Biochem J","first-page":"75","article-title":"The central role of mosquito cytochrome P450 CYP6Zs in insecticide detoxification revealed by functional expression and structural modelling","volume":"455","author":"Chandor-Proust","year":"2013"},{"key":"b21","series-title":"Insect Mol Biol","first-page":"379","article-title":"Genetic mapping of genes conferring permethrin resistance in the malaria vector, Anopheles gambiae","volume":"13","author":"Ranson","year":"2004"},{"key":"b22","series-title":"Neotrop Entomol","first-page":"1","article-title":"Insecticidal gene silencing by RNAi in the neotropical region","volume":"49","author":"Dias","year":"2020"},{"key":"b23","series-title":"PLoS Negl Trop Dis","first-page":"e0005302","article-title":"Pyrethroid resistance in Malaysian populations of dengue vector Aedes aegypti is mediated by CYP9 family of cytochrome P450 genes","volume":"11","author":"Ishak","year":"2017"},{"key":"b24","series-title":"J Med Entomol","first-page":"817","article-title":"Cytochrome P450 mono-oxygenase and resistance phenotype in DDT and deltamethrin-resistant Anopheles gambiae (Diptera: Culicidae) and Culex quinquefasciatus in Kosofe, Lagos, Nigeria","volume":"56","author":"Fagbohun","year":"2019"},{"key":"b25","series-title":"Pestic Biochem Physiol","first-page":"104783","article-title":"Detection of kdr and ace-1 mutations in wild populations of Anopheles arabiensis and An. melas in a residual malaria transmission area of Senegal","volume":"173","author":"Sy","year":"2021"},{"key":"b26","series-title":"Pest Manag Sci","first-page":"4127","article-title":"Glutathione S-transferase (GST) genes and their function associated with pyrethroid resistance in the malaria vector Anopheles sinensis","volume":"78","author":"Tao","year":"2022"},{"key":"b27","series-title":"Proc Natl Acad Sci USA","first-page":"4619","article-title":"Rapid selection of a pyrethroid metabolic enzyme CYP9K1 by operational malaria control activities","volume":"115","author":"Vontas","year":"2018"},{"key":"b28","series-title":"Nat Protoc","first-page":"1101","article-title":"Analyzing real-time PCR data by the comparative C(T) method","volume":"3","author":"Schmittgen","year":"2008"},{"key":"b29","series-title":"Pest Manag Sci","first-page":"877","article-title":"The molecular interactions of pyrethroid insecticides with insect and mammalian sodium channels","volume":"57","author":"Vais","year":"2001"},{"key":"b30","series-title":"Pest Manag Sci","first-page":"861","article-title":"English field samples of Thrips tabaci show strong and ubiquitous resistance to deltamethrin","volume":"66","author":"Foster","year":"2010"},{"key":"b31","series-title":"PLoS Negl Trop Dis","first-page":"e2948","article-title":"Mechanisms of pyrethroid resistance in the dengue mosquito vector, Aedes aegypti: target site insensitivity, penetration, and metabolism","volume":"8","author":"Kasai","year":"2014"},{"key":"b32","series-title":"Proc Natl Acad Sci USA","first-page":"25764","article-title":"Functional genetic validation of key genes conferring insecticide resistance in the major African malaria vector, Anopheles gambiae","volume":"116","author":"Adolfi","year":"2019"},{"key":"b33","series-title":"Pest Manag Sci","first-page":"886","article-title":"Gene amplification and insecticide resistance","volume":"67","author":"Bass","year":"2011"},{"key":"b34","series-title":"Annu Rev Entomol","first-page":"231","article-title":"Molecular mechanisms of metabolic resistance to synthetic and natural xenobiotics","volume":"52","author":"Li","year":"2007"},{"key":"b35","series-title":"J Med Entomol","first-page":"605","article-title":"Transcriptional analysis of four family 4 P450s in a Puerto Rico strain of Aedes aegypti (Diptera: Culicidae) compared with an Orlando strain and their possible functional roles in permethrin resistance","volume":"51","author":"Reid","year":"2014"},{"key":"b36","series-title":"PLoS Negl Trop Dis","first-page":"e1692","article-title":"Gene amplification, ABC transporters and cytochrome P450s: unraveling the molecular basis of pyrethroid resistance in the dengue vector, Aedes aegypti.","volume":"6","author":"Bariami","year":"2012"},{"key":"b37","series-title":"Pest Manag Sci","first-page":"2744","article-title":"CYP4BN6 and CYP6BQ11 mediate insecticide susceptibility and their expression is regulated by Latrophilin in Tribolium castaneum","volume":"75","author":"Xiong","year":"2019"},{"key":"b38","series-title":"BMC Genomics","first-page":"538","article-title":"Expression of the cytochrome P450s, CYP6P3 and CYP6M2 are significantly elevated in multiple pyrethroid resistant populations of Anopheles gambiae s.s. from Southern Benin and Nigeria","volume":"9","author":"Djouaka","year":"2008"},{"key":"b39","series-title":"J Biol Chem","first-page":"1671","article-title":"Cytochrome P450 research and The Journal of Biological Chemistry","volume":"294","author":"Guengerich","year":"2019"},{"key":"b40","series-title":"Insect Biochem Mol Biol","first-page":"23","article-title":"The cytochrome P450 CYP6P4 is responsible for the high pyrethroid resistance in knockdown resistance-free Anopheles arabiensis","volume":"68","author":"Ibrahim","year":"2016"},{"key":"b41","series-title":"Genes (Basel)","first-page":"1403","article-title":"Insecticide resistance profiling of Anopheles coluzzii and Anopheles gambiae populations in the southern Senegal: role of target sites and metabolic resistance mechanisms","volume":"11","author":"Gueye","year":"2020"},{"key":"b42","series-title":"Pest Manag Sci","first-page":"1265","article-title":"Deltamethrin is metabolized by CYP6FU1, a cytochrome P450 associated with pyrethroid resistance, in Laodelphax striatellus","volume":"74","author":"Elzaki","year":"2018"},{"key":"b43","series-title":"Arch Insect Biochem Physiol","first-page":"e21525","article-title":"An overexpressed cytochrome P450 CYP439A1v3 confers deltamethrin resistance in Laodelphax striatellus Fall\u00e9n (Hemiptera: Delphacidae)","volume":"100","author":"Miah","year":"2019"},{"key":"b44","series-title":"Parasit Vectors","first-page":"335","article-title":"Insecticide resistance status of Anopheles arabiensis in irrigated and non-irrigated areas in western Kenya","volume":"14","author":"Orondo","year":"2021"},{"key":"b45","series-title":"Genes (Basel)","first-page":"140","article-title":"Pyrethroid resistance in the major malaria vector Anopheles funestus is exacerbated by overexpression and overactivity of the P450 CYP6AA1 across Africa","volume":"9","author":"Ibrahim","year":"2018"},{"key":"b46","series-title":"J Insect Sci","first-page":"12","article-title":"Delivery methods for RNAi in mosquito larvae","volume":"20","author":"Munawar","year":"2020"},{"key":"b47","series-title":"Curr Opin Insect Sci","first-page":"18","article-title":"Advances in oral RNAi for disease vector mosquito research and control","volume":"40","author":"Wiltshire","year":"2020"},{"key":"b48","series-title":"Parasit Vectors","first-page":"96","article-title":"Silencing the buzz: a new approach to population suppression of mosquitoes by feeding larvae double-stranded RNAs","volume":"8","author":"Whyard","year":"2015"},{"key":"b49","series-title":"PeerJ","first-page":"e2673","article-title":"RNA interference as a gene silencing tool to control Tuta absoluta in tomato (Solanum lycopersicum)","volume":"4","author":"Camargo","year":"2016"},{"key":"b50","series-title":"Curr Opin Insect Sci","first-page":"61","article-title":"Harnessing model organisms to study insecticide resistance","volume":"27","author":"Perry","year":"2018"},{"key":"b51","series-title":"Am J Trop Med Hyg","first-page":"277","article-title":"Pyrethroid resistance in Aedes aegypti from Grand Cayman","volume":"83","author":"Harris","year":"2010"},{"key":"b52","series-title":"Pestic Biochem Physiol","first-page":"119","article-title":"CYP-mediated resistance and cross-resistance to pyrethroids and organophosphates in Aedes aegypti in the presence and absence of kdr","volume":"160","author":"Smith","year":"2019"}],"container-title":["The American Journal of Tropical Medicine and 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