single mutation in the GSTe2 gene allows tracking of metabolically based insecticide resistance in a major malaria vector

BACKGROUND: Metabolic resistance to insecticides is the biggest threat to the continued effectiveness of malaria vector control. However, its underlying molecular basis, crucial for successful resistance management, remains poorly characterized. RESULTS: Here, we demonstrate that the single amino ac...

Celý popis

Uložené v:

Podrobná bibliografia
Vydané v:	Genome biology Ročník 15; číslo 2; s. R27 - 27
Hlavní autori:	Riveron, Jacob M, Yunta, Cristina, Ibrahim, Sulaiman S, Djouaka, Rousseau, Irving, Helen, Menze, Benjamin D, Ismail, Hanafy M, Hemingway, Janet, Ranson, Hilary, Albert, Armando, Wondji, Charles S
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Springer-Verlag 25.02.2014 BioMed Central
Predmet:	Africa Alleles Animal Genetics and Genomics Animals Anopheles - drug effects Anopheles - genetics Anopheles funestus Benin Bioinformatics Biomedical and Life Sciences cross resistance Crystallography, X-Ray DDT (pesticide) DDT - toxicity Drosophila melanogaster evolution Evolutionary Biology gene expression regulation gene flow gene overexpression genes geographical distribution glutathione transferase Glutathione Transferase - chemistry Glutathione Transferase - genetics Human Genetics Humans Insect Vectors - drug effects Insect Vectors - genetics insecticide resistance Insecticide Resistance - genetics Life Sciences malaria Malaria - genetics Malaria - transmission Microbial Genetics and Genomics Molecular Sequence Data Mutation permethrin Plant Genetics and Genomics point mutation Pyrethrins - metabolism resistance management vector control Benin Africa Root Mean Square Deviation Pyrethroid Resistance Indoor Residual Spray Deltamethrin L119F Mutation
ISSN:	1465-6906, 1474-760X, 1465-6914, 1474-760X
On-line prístup:	Získať plný text
Tagy:	Pridať tag Žiadne tagy, Buďte prvý, kto otaguje tento záznam!

Popis
Shrnutí:	BACKGROUND: Metabolic resistance to insecticides is the biggest threat to the continued effectiveness of malaria vector control. However, its underlying molecular basis, crucial for successful resistance management, remains poorly characterized. RESULTS: Here, we demonstrate that the single amino acid change L119F in an upregulated glutathione S-transferase gene, GSTe2, confers high levels of metabolic resistance to DDT in the malaria vector Anopheles funestus. Genome-wide transcription analysis revealed that GSTe2 was the most over-expressed detoxification gene in DDT and permethrin-resistant mosquitoes from Benin. Transgenic expression of GSTe2 in Drosophila melanogaster demonstrated that over-transcription of this gene alone confers DDT resistance and cross-resistance to pyrethroids. Analysis of GSTe2 polymorphism established that the point mutation is tightly associated with metabolic resistance to DDT and its geographical distribution strongly correlates with DDT resistance patterns across Africa. Functional characterization of recombinant GSTe2 further supports the role of the L119F mutation, with the resistant allele being more efficient at metabolizing DDT than the susceptible one. Importantly, we also show that GSTe2 directly metabolizes the pyrethroid permethrin. Structural analysis reveals that the mutation confers resistance by enlarging the GSTe2 DDT-binding cavity, leading to increased DDT access and metabolism. Furthermore, we show that GSTe2 is under strong directional selection in resistant populations, and a restriction of gene flow is observed between African regions, enabling the prediction of the future spread of this resistance. CONCLUSIONS: This first DNA-based metabolic resistance marker in mosquitoes provides an essential tool to track the evolution of resistance and to design suitable resistance management strategies.
Bibliografia:	http://dx.doi.org/10.1186/gb-2014-15-2-r27 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1465-6906 1474-760X 1465-6914 1474-760X
DOI:	10.1186/gb-2014-15-2-r27