The Central Role of Multiple P450 Genes and Their Co-factor CPR in the Development of Permethrin Resistance in the Mosquito Culex quinquefasciatus

Gong, Youhui; Li, Ting; Li, Qi; Liu, Shikai; Liu, Nannan

doi:10.3389/fphys.2021.802584

Cited by 6 publications

(5 citation statements)

References 59 publications

(135 reference statements)

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“…For instance, CYP9J33 , CYP9J40 , and CYP9J45 are overexpressed and demonstrate the ability to metabolize insecticide in permethrin‐resistant Cx. quinquefasciatu s 48 . In addition, the expression level of CYP9M5 increased 54‐fold in resistant strains of Aedes aegypti 24 .…”

Section: Discussionmentioning

confidence: 99%

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Transcription factor B‐H2 regulates CYP9J34 expression conveying deltamethrin resistance in Culex pipiens pallens

Du,

Yin,

et al. 2024

Pest Management Science

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BackgroundMosquitoes are vectors of various diseases, posing significant health threats worldwide. Chemical pesticides, particularly pyrethroids like deltamethrin, are commonly used for mosquito control, but the emergence of resistant mosquito populations has become a concern. In the deltamethrin‐resistant strain of Culex pipiens pallens, the highly expressed cytochrome P450 9J34 (CYP9J34) gene is believed to play a role in resistance, yet the underlying mechanism remains unclear.ResultsqRT‐PCR analysis revealed that the expression of CYP9J34 was 14.6‐fold higher in deltamethrin‐resistant (DR) than in deltamethrin‐susceptible (DS) strains. The recombinant production of CYP9J34 protein of Cx. pipiens pallens showed that the protein could directly metabolize deltamethrin, yielding the major metabolite 4'‐OH deltamethrin. Through dual luciferase reporter assays and RNA interference, the transcription factor homeobox protein B‐H2‐like (B‐H2) was identified to modulate the expression of the CYP9J34 gene, contributing to mosquito resistance to deltamethrin.ConclusionsOur findings demonstrate that the CYP9J34 protein could directly degrade deltamethrin, and the transcription factor B‐H2 could regulate the CYP9J34 expression, influencing the resistance of mosquitoes to deltamethrin.This article is protected by copyright. All rights reserved.

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Section: Discussionmentioning

confidence: 99%

“…quinquefasciatus. 48 In addition, the expression level of CYP9M5 increased 54-fold in resistant strains of Aedes aegypti. 24 Moreover, previous studies have identified that deltamethrin can be metabolized by Anopheles gambiae-resistant strains CYP9K1 and CYP9J5.…”

Section: Discussionmentioning

confidence: 99%

Transcription factor B‐H2 regulates CYP9J34 expression conveying deltamethrin resistance in Culex pipiens pallens

Du,

Yin,

et al. 2024

Pest Management Science

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“…Cpr , also known as NADPH cytochrome P450 reductase (AGAP000500), is an essential electron donor in P450-mediated reactions, including insecticide metabolism. Increased Cpr expression has been implicated in insecticide resistance in Culex (Gong et al ., 2022), and knockdown of the gene has been demonstrated to elevate permethrin susceptibility in An. gambaie (Lycett et al ., 2006).…”

Section: Discussionmentioning

confidence: 99%

Cryptic population structure and insecticide resistance inAnopheles gambiaefrom the southern Democratic Republic of Congo

Dennis,

Pescod,

Barasa

et al. 2024

Preprint

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The Democratic Republic of Congo (DRC) suffers from one of the highest malaria burdens worldwide, but information on its Anopheles vector populations is relatively limited. Preventative malaria control in DRC is reliant on pyrethroid-treated nets, raising concerns over the potential impacts of insecticide resistance. We sampled Anopheles gambiae from three geographically distinct populations (Kimpese, Kapolowe and Mikalayi) in southern DRC, collecting from three sub-sites per population and characterising mosquito collections from each for resistance to pyrethroids using WHO tube bioassays. Resistance to each of three different pyrethroids was generally high in An. gambiae with <92% mortality in all tests, but varied between collections, with mosquitoes from Kimpese being the most resistant. Whole genome sequencing of 165 An. gambiae revealed evidence for genetic differentiation between Kimpese and Kapolowe / Mikalayi, but not between the latter two sample sites despite separation of approximately 800km. Surprisingly, there was evidence of population structure at a small spatial scale between collection subsites in Kimpese, despite separation of just tens of kilometres. Intra-population (H12) and inter-population (FST) genome scans identified multiple peaks corresponding to genes associated with insecticide resistance such as the voltage gated sodium channel (Vgsc) target site on chromosome 2L, a Cyp6 cytochrome P450 cluster on chromosome arm 2R, and the Cyp9k1 P450 gene on chromosome X. In addition, in the Kimpese subsites, the P450 redox partner gene Cpr showed evidence for contemporary selection (H12) and population differentiation (FST) meriting further exploration as a potential resistance associated marker.

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“…The NADPH cytochrome P450 reductase is also an electron transfer protein found in the endoplasmic reticulum of cells. NADPH cytochrome P450 reductase and cytb5 have been co-expressed in some instances [ 41 ]. Marcombe et al [ 42 ] have reported the overexpression of NADPH cytochrome P450 reductase in insecticide-resistant Ae .…”

Section: Discussionmentioning

confidence: 99%

Quantitative proteomics analysis of permethrin and temephos-resistant Ae. aegypti revealed diverse differentially expressed proteins associated with insecticide resistance from Penang Island, Malaysia

Shettima,

Ishak,

Lau

et al. 2023

PLoS Negl Trop Dis

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Synthetic insecticides are the primary vector control method used globally. However, the widespread use of insecticides is a major cause of insecticide-resistance in mosquitoes. Hence, this study aimed at elucidating permethrin and temephos-resistant protein expression profiles in Ae. aegypti using quantitative proteomics. In this study, we evaluated the susceptibility of Ae. aegypti from Penang Island dengue hotspot and non-hotspot against 0.75% permethrin and 31.25 mg/l temephos using WHO bioassay method. Protein extracts from the mosquitoes were then analysed using LC–ESI–MS/MS for protein identification and quantification via label-free quantitative proteomics (LFQ). Next, Perseus 1.6.14.0 statistical software was used to perform differential protein expression analysis using ANOVA and Student’s t-test. The t-test selected proteins with≥2.0-fold change (FC) and ≥2 unique peptides for gene expression validation via qPCR. Finally, STRING software was used for functional ontology enrichment and protein-protein interactions (PPI). The WHO bioassay showed resistance with 28% and 53% mortalities in adult mosquitoes exposed to permethrin from the hotspot and non-hotspot areas. Meanwhile, the susceptibility of Ae. aegypti larvae revealed high resistance to temephos in hotspot and non-hotspot regions with 80% and 91% mortalities. The LFQ analyses revealed 501 and 557 (q-value <0.05) differentially expressed proteins in adults and larvae Ae. aegypti. The t-test showed 114 upregulated and 74 downregulated proteins in adult resistant versus laboratory strains exposed to permethrin. Meanwhile, 13 upregulated and 105 downregulated proteins were observed in larvae resistant versus laboratory strains exposed to temephos. The t-test revealed the upregulation of sodium/potassium-dependent ATPase β2 in adult permethrin resistant strain, H15 domain-containing protein, 60S ribosomal protein, and PB protein in larvae temephos resistant strain. The downregulation of troponin I, enolase phosphatase E1, glucosidase 2β was observed in adult permethrin resistant strain and tubulin β chain in larvae temephos resistant strain. Furthermore, the gene expression by qPCR revealed similar gene expression patterns in the above eight differentially expressed proteins. The PPI of differentially expressed proteins showed a p-value at <1.0 x 10−16 in permethrin and temephos resistant Ae. aegypti. Significantly enriched pathways in differentially expressed proteins revealed metabolic pathways, oxidative phosphorylation, carbon metabolism, biosynthesis of amino acids, glycolysis, and citrate cycle. In conclusion, this study has shown differentially expressed proteins and highlighted upregulated and downregulated proteins associated with insecticide resistance in Ae. aegypti. The validated differentially expressed proteins merit further investigation as a potential protein marker to monitor and predict insecticide resistance in field Ae. aegypti. The LC-MS/MS data were submitted into the MASSIVE database with identifier no: MSV000089259.

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The Central Role of Multiple P450 Genes and Their Co-factor CPR in the Development of Permethrin Resistance in the Mosquito Culex quinquefasciatus

Cited by 6 publications

References 59 publications

Transcription factor B‐H2 regulates CYP9J34 expression conveying deltamethrin resistance in Culex pipiens pallens

Transcription factor B‐H2 regulates CYP9J34 expression conveying deltamethrin resistance in Culex pipiens pallens

Cryptic population structure and insecticide resistance inAnopheles gambiaefrom the southern Democratic Republic of Congo

Quantitative proteomics analysis of permethrin and temephos-resistant Ae. aegypti revealed diverse differentially expressed proteins associated with insecticide resistance from Penang Island, Malaysia

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