Cytochrome P450 associated with insecticide resistance catalyzes cuticular hydrocarbon production in Anopheles gambiae.

Published on Aug 16, 2016in Proceedings of the National Academy of Sciences of the United States of America9.58
· DOI :10.1073/PNAS.1608295113
Vasileia Balabanidou7
Estimated H-index: 7
(FORTH: Foundation for Research & Technology – Hellas),
Anastasia Kampouraki6
Estimated H-index: 6
(UoC: University of Crete)
+ 12 AuthorsJohn Vontas44
Estimated H-index: 44
(FORTH: Foundation for Research & Technology – Hellas)
The role of cuticle changes in insecticide resistance in the major malaria vector Anopheles gambiae was assessed. The rate of internalization of 14C deltamethrin was significantly slower in a resistant strain than in a susceptible strain. Topical application of an acetone insecticide formulation to circumvent lipid-based uptake barriers decreased the resistance ratio by ∼50%. Cuticle analysis by electron microscopy and characterization of lipid extracts indicated that resistant mosquitoes had a thicker epicuticular layer and a significant increase in cuticular hydrocarbon (CHC) content (∼29%). However, the CHC profile and relative distribution were similar in resistant and susceptible insects. The cellular localization and in vitro activity of two P450 enzymes, CYP4G16 and CYP4G17, whose genes are frequently overexpressed in resistant Anopheles mosquitoes, were analyzed. These enzymes are potential orthologs of the CYP4G1/2 enzymes that catalyze the final step of CHC biosynthesis in Drosophila and Musca domestica, respectively. Immunostaining indicated that both CYP4G16 and CYP4G17 are highly abundant in oenocytes, the insect cell type thought to secrete hydrocarbons. However, an intriguing difference was indicated; CYP4G17 occurs throughout the cell, as expected for a microsomal P450, but CYP4G16 localizes to the periphery of the cell and lies on the cytoplasmic side of the cell membrane, a unique position for a P450 enzyme. CYP4G16 and CYP4G17 were functionally expressed in insect cells. CYP4G16 produced hydrocarbons from a C18 aldehyde substrate and thus has bona fide decarbonylase activity similar to that of dmCYP4G1/2. The data support the hypothesis that the coevolution of multiple mechanisms, including cuticular barriers, has occurred in highly pyrethroid-resistant An. gambiae.
  • References (44)
  • Citations (97)
📖 Papers frequently viewed together
214 Citations
189 Citations
309 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Janet Hemingway (LSTM: Liverpool School of Tropical Medicine)H-Index: 72
#2Hilary Ranson (LSTM: Liverpool School of Tropical Medicine)H-Index: 69
Last. Nicholas HamonH-Index: 3
view all 15 authors...
World Malaria Day 2015 highlighted the progress made in the development of new methods of prevention (vaccines and insecticides) and treatment (single dose drugs) of the disease. However, increasing drug and insecticide resistance threatens the successes made with existing methods. Insecticide resistance has decreased the efficacy of the most commonly used insecticide class of pyrethroids. This decreased efficacy has increased mosquito survival, which is a prelude to rising incidence of malaria ...
161 CitationsSource
#1Hilary Ranson (LSTM: Liverpool School of Tropical Medicine)H-Index: 69
#2Natalie Lissenden (LSTM: Liverpool School of Tropical Medicine)H-Index: 4
Malaria control is reliant on insecticides to control the mosquito vector. As efforts to control the disease have intensified, so has the selection pressure on mosquitoes to develop resistance to these insecticides. The distribution and strength of this resistance has increased dramatically in recent years and now threatens the success of control programs. This review provides an update on the current status of resistance to the major insecticide classes in African malaria vectors, considers the...
309 CitationsSource
#1Henry Chung (HHMI: Howard Hughes Medical Institute)H-Index: 15
#2Sean B. Carroll (HHMI: Howard Hughes Medical Institute)H-Index: 82
Evolutionary changes in traits that affect both ecological divergence and mating signals could lead to reproductive isolation and the formation of new species. Insect cuticular hydrocarbons (CHCs) are potential examples of such dual traits. They form a waxy layer on the cuticle of the insect to maintain water balance and prevent desiccation, while also acting as signaling molecules in mate recognition and chemical communication. Because the synthesis of these hydrocarbons in insect oenocytes occ...
110 CitationsSource
Intraspecific olfactory signals known as pheromones play important roles in insect mating systems. In the model Drosophila melanogaster, a key part of the pheromone-detecting system has remained enigmatic through many years of research in terms of both its behavioral significance and its activating ligands. Here we show that Or47b-and Or88a-expressing olfactory sensory neurons (OSNs) detect the fly-produced odorants methyl laurate (ML), methyl myristate, and methyl palmitate. Fruitless (fruM)-po...
130 CitationsSource
#1Kobié H. Toé (LSTM: Liverpool School of Tropical Medicine)H-Index: 3
#2Sagnon N’FaleH-Index: 5
Last. Christopher M. Jones (LSTM: Liverpool School of Tropical Medicine)H-Index: 22
view all 5 authors...
Background: Since 2011, the level of pyrethroid resistance in the major malaria mosquito, Anopheles coluzzi, has increased to such an extent in Burkina Faso that none of the long lasting insecticide treated nets (LLINs) currently in use throughout the country kill the local mosquito vectors. We investigated whether this observed increase was associated with transcriptional changes in field-caught Anopheles coluzzi using two independent whole-genome microarray studies, performed in 2011 and 2012....
44 CitationsSource
#1Nannan Liu (AU: Auburn University)H-Index: 30
Mosquito-borne diseases, the most well known of which is malaria, are among the leading causes of human deaths worldwide. Vector control is a very important part of the global strategy for management of mosquito-associated diseases, and insecticide application is the most important component in this effort. However, mosquito-borne diseases are now resurgent, largely because of the insecticide resistance that has developed in mosquito vectors and the drug resistance of pathogens. A large number o...
240 CitationsSource
#1Victoria A Ingham (Warw.: University of Warwick)H-Index: 5
#2Christopher M. Jones (LSTM: Liverpool School of Tropical Medicine)H-Index: 22
Last. Hilary Ranson (LSTM: Liverpool School of Tropical Medicine)H-Index: 69
view all 8 authors...
Background: The elevated expression of enzymes with insecticide metabolism activity can lead to high levels of insecticide resistance in the malaria vector, Anopheles gambiae. In this study, adult female mosquitoes from an insecticide susceptible and resistant strain were dissected into four different body parts. RNA from each of these samples was used in microarray analysis to determine the enrichment patterns of the key detoxification gene families within the mosquito and to identify additiona...
30 CitationsSource
#1Kobié H. ToéH-Index: 3
Last. Hilary RansonH-Index: 69
view all 6 authors...
Malaria control is dependent on insecticides. Increases in prevalence of insecticide resistance in malaria vectors across Africa are well-documented. However, few attempts have been made to quantify the strength of this resistance and link it to the effectiveness of control tools. Using quantitative bioassays, we show that in Burkina Faso pyrethroid resistance in Anopheles gambiae mosquitoes has increased in intensity in recent years and now exceeds 1,000-fold. In laboratory assays, this level o...
107 CitationsSource
Venezuela had the highest number of human malaria cases in Latin American before 1936. During 1891–1920, malaria was endemic to >600,000 km2 of this country; malaria death rates led to major population decreases during 1891–1920. No pathogen, including the influenza virus that caused the 1918 pandemic, caused more deaths than malaria during 1905–1945. Early reports of malaria eradication in Venezuela helped spark the world’s interest in global eradication. We describe early approaches to malaria...
43 CitationsSource
#1Rami Makki (NIMR: National Institute for Medical Research)H-Index: 2
#2Einat CinnamonH-Index: 8
Last. Alex P. Gould (Medical Research Council)H-Index: 32
view all 3 authors...
Oenocytes have intrigued insect physiologists since the nineteenth century. Many years of careful but mostly descriptive research on these cells highlights their diverse sizes, numbers, and anatomical distributions across Insecta. Contemporary molecular genetic studies in Drosophila melanogaster and Tribolium castaneum support the hypothesis that oenocytes are of ectodermal origin. They also suggest that, in both short and long germ-band species, oenocytes are induced from a Spalt major/Engraile...
71 CitationsSource
Cited By97
#1Qiuyan Zhu (GDUT: Guangdong University of Technology)H-Index: 2
#2Yang Yang (GDUT: Guangdong University of Technology)H-Index: 2
Last. Suqing Zhao (GDUT: Guangdong University of Technology)H-Index: 9
view all 8 authors...
Abstract Pyrethroids are a class of highly effective, broad-spectrum, less toxic, biodegradable synthetic pesticides. However, despite the extremely wide application of pyrethroids, there are many problems, such as insecticide resistance, lethal/sub-lethal toxicity to mammals, aquatic organisms or other beneficial organisms. The objectives of this review were to cover the main structures, synthesis, steroisomers, mechanisms of action, anti-mosquito activities, resistance, photodegradation and to...
#1Yiyan ZhaoH-Index: 1
#2Weimin LiuH-Index: 3
Last. Jianzhen ZhangH-Index: 26
view all 9 authors...
#1Hui Xiong (ECUST: East China University of Science and Technology)H-Index: 1
#2Xuefeng Liu (ECUST: East China University of Science and Technology)
Last. Qingchun Huang (ECUST: East China University of Science and Technology)H-Index: 8
view all 6 authors...
Benzoylphenylureas as an important type of insect growth regulators, acting on the moulting stage in immature insects, are highly effective and low toxic. The new benzoylphenylurea TXH09 [N-((2,6-dimethyl-4-(heptafluoropropyl-2-yl)phenyl)carbamoyl)-2,6-difluorobenzami de] has high efficacy against chewing insect pests harming vegetables and rice. In this paper, the efficacy of TXH09 against two intractable borers Ostrinia furnacalis and Grapholitha molesta were evaluated in field, and safety ass...
#1Lixian Wu (Shanxi University)H-Index: 1
#2Zhitao Yu (Shanxi University)H-Index: 4
Last. Jianzhen Zhang (Shanxi University)H-Index: 26
view all 9 authors...
Abstract Cytochrome P450 monooxygenases (CYPs) serve many functions in insects, from the regulation of development to xenobiotic detoxification. Several conserved CYPs have been shown to play a role in insect growth and development. CYP303A1 is a highly conserved CYP with a single ortholog in most insects, but its underlying molecular characteristics and specific physiological functions remain poorly understood. In Drosophila melanogaster and Locusta migratoria, CYP303A1 is indispensable for ecl...
#1Linda Grigoraki (LSTM: Liverpool School of Tropical Medicine)H-Index: 8
#2Xavier Grau-Bové (LSTM: Liverpool School of Tropical Medicine)H-Index: 10
Last. Hilary Ranson (LSTM: Liverpool School of Tropical Medicine)H-Index: 69
view all 5 authors...
The surface of insects is coated in cuticular hydrocarbons (CHCs); variations in the composition of this layer affect a range of traits including adaptation to arid environments and defence against pathogens and toxins. In the African malaria vector, Anopheles gambiae quantitative and qualitative variance in CHC composition have been associated with speciation, ecological habitat and insecticide resistance. Understanding how these modifications arise will inform us of how mosquitoes are respondi...
#1Bowen Wang (NEFU: Northeast Forestry University)H-Index: 2
#2Xin Hao (NEFU: Northeast Forestry University)H-Index: 2
Last. Ling Ma (NEFU: Northeast Forestry University)H-Index: 5
view all 7 authors...
Pine wood nematode (Bursaphelenchus xylophilus, PWN) is a devastating invasive species which is expanding into colder regions. Here, we investigated the molecular mechanisms underlying low temperature resistance of PWN. We identified differentially expressed genes (DEGs) enriched under low temperature in previously published transcriptome data using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Quantitative real-time Polymerase Chain Reaction (qRT-PCR) was utilized to further validate the ...
#1Ronise Silva (Bandim Health Project)
#2Konstantinos Mavridis (FORTH: Foundation for Research & Technology – Hellas)H-Index: 15
Last. Hugo Osório (University of Lisbon)
view all 5 authors...
Abstract Despite reduction in the prevalence of malaria, Guinea-Bissau (GB) is still widely affected by the disease that is primarily vectored by Anopheles gambiae s.l. mosquitoes. Monitoring mosquito susceptibility and investigating the insecticide resistance status is an integral part of malaria control actions. Here, mosquito populations from five regions of GB: Bafata, Bissau, Buba, Cacheu and Gabu were monitored for species ID and insecticide resistance, using diagnostic and intensity WHO b...
#1Faye Brown (LSTM: Liverpool School of Tropical Medicine)H-Index: 1
#2Douglas G. Paton (Harvard University)H-Index: 2
Last. Victoria A Ingham (LSTM: Liverpool School of Tropical Medicine)H-Index: 5
view all 5 authors...
Insecticide based vector control tools such as insecticide treated bednets and indoor residual spraying represent the cornerstones of malaria control programs. Resistance to chemistries used in these programs is now widespread and represents a significant threat to the gains seen in reducing malaria-related morbidity and mortality. Recently, disruption of the 20-hydroxyecdysone steroid hormone pathway was shown to reduce Plasmodium development and significantly reduce both longevity and egg prod...
#1Lixian Wu (Shanxi University)H-Index: 1
#2Zhan-Feng Zhang (NWAFU: Northwest A&F University)H-Index: 7
Last. Jianzhen Zhang (Shanxi University)H-Index: 26
view all 10 authors...
BACKGROUND: Cuticular hydrocarbons (CHCs) play a critical role to prevent desiccation and penetration of xenobiotics in insects. Previous studies have shown that cytochrome P450 subfamily 4G (CYP4G) enzymes are oxidative decarbonylases, essential for CHC biosynthesis. However, it is unclear whether there are functional differences between the two CYP4G genes in most insects. In Locusta migratoria, we have identified two CYP4G genes (LmCYP4G62 and LmCYP4G102). LmCYP4G102 plays a critical role in ...
#1Tian-Xing Jing (SWU: Southwest University)H-Index: 4
#2Di‐Fei Wang (SWU: Southwest University)
Last. Jinjun Wang (SWU: Southwest University)H-Index: 32
view all 8 authors...
BACKGROUND: Bactrocera dorsalis (Hendel) is a notorious agricultural pest worldwide, and its resistance to insecticides is a major obstacle in successful control. Cytochrome P450s (P450s) are major metabolic enzymes associated with insecticide resistance. The genome of B. dorsalis was recently sequenced, allowing an integrated genome-wide analysis of P450 genes and the analysis of correlations between these genes and insecticide resistance in this pest. RESULTS: Totally, 101 P450 genes were iden...