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

Riveron Miranda, Jacob ORCID: https://orcid.org/0000-0002-5395-767X, Yunta Yanes, Cristina, Ibrahim, SulaimanSadi, Djouaka, Rousseau, Irving, Helen, Menze, Benjamin D., Ismail, Hanafy ORCID: https://orcid.org/0000-0002-9953-9588, Hemingway, Janet ORCID: https://orcid.org/0000-0002-3200-7173, Ranson, Hilary ORCID: https://orcid.org/0000-0003-2332-8247, Albert, Armando and Wondji, Charles ORCID: https://orcid.org/0000-0003-0791-3673 (2014) 'A single mutation in the GSTe2 gene allows tracking of metabolically-based insecticide resistance in a major malaria vector'. Genome Biology, Vol 15, Issue 2, R27.

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Abstract

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.

Item Type:	Article
Subjects:	QU Biochemistry > Proteins. Amino Acids. Peptides > QU 58.5 DNA. QX Parasitology > Insects. Other Parasites > QX 515 Anopheles QX Parasitology > Insects. Other Parasites > QX 600 Insect control. Tick control WA Public Health > Preventive Medicine > WA 240 Disinfection. Disinfestation. Pesticides (including diseases caused by) WC Communicable Diseases > Tropical and Parasitic Diseases > WC 765 Prevention and control
Faculty: Department:	Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.1186/gb-2014-15-2-r27
Depositing User:	Martin Chapman
Date Deposited:	25 Feb 2014 12:15
Last Modified:	17 Aug 2022 08:57
URI:	https://archive.lstmed.ac.uk/id/eprint/3589

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