A brain-specific cytochrome P450 responsible for the majority of deltamethrin resistance in the QTC279 strain of Tribolium castaneum

Fang Zhu, R. Parthasarathy, Hua Bai, Katharina Woithe, Martin Kaussmann, Ralf Nauen, Douglas A. Harrison, Subba R. Palli

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

Cytochrome P450-mediated detoxification is one of the most important mechanisms involved in insecticide resistance. However, the molecular basis of this mechanism and the physiological functions of P450s associated with insecticide resistance remain largely unknown. Here, we exploited the functional genomics and reverse genetic approaches to identify and characterize a P450 gene responsible for the majority of deltamethrin resistance observed in the QTC279 strain of Tribolium castaneum. We used recently completed whole-genome sequence of T. castaneum to prepare custom microarrays and identified a P450 gene, CYP6BQ9, which showed more than a 200-fold higher expression in the deltamethrin-resistant QTC279 strain when compared with its expression in the deltamethrin-susceptible Lab-S strain. Functional studies using both double-strand RNA (dsRNA)-mediated knockdown in the expression of CYP6BQ9 and transgenic expression of CYP6BQ9 in Drosophila melanogaster showed that CYP6BQ9 confers deltamethrin resistance. Furthermore, CYP6BQ9 enzyme expressed in baculovirus metabolizes deltamethrin to 4-hydroxy deltamethrin. Strikingly, we also found that unlike many P450 genes involved in insecticide resistance that were reported previously, CYP6BQ9 is predominantly expressed in the brain, a part of the central nervous system (CNS) containing voltage-gated sodium channels targeted by deltamethrin. Taken together, the current studies on the brain-specific insect P450 involved in delta-methrin resistance shed new light on the understanding of the molecular basis and evolution of insecticide resistance.

Original languageEnglish (US)
Pages (from-to)8557-8562
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number19
DOIs
StatePublished - May 11 2010

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Tribolium
Cytochrome P-450 Enzyme System
Insecticide Resistance
Brain
Genes
Voltage-Gated Sodium Channels
Reverse Genetics
Molecular Evolution
Baculoviridae
Genomics
decamethrin
Drosophila melanogaster
Insects
Central Nervous System
Genome
RNA
Enzymes

All Science Journal Classification (ASJC) codes

  • General

Cite this

Zhu, Fang ; Parthasarathy, R. ; Bai, Hua ; Woithe, Katharina ; Kaussmann, Martin ; Nauen, Ralf ; Harrison, Douglas A. ; Palli, Subba R. / A brain-specific cytochrome P450 responsible for the majority of deltamethrin resistance in the QTC279 strain of Tribolium castaneum. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 19. pp. 8557-8562.
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A brain-specific cytochrome P450 responsible for the majority of deltamethrin resistance in the QTC279 strain of Tribolium castaneum. / Zhu, Fang; Parthasarathy, R.; Bai, Hua; Woithe, Katharina; Kaussmann, Martin; Nauen, Ralf; Harrison, Douglas A.; Palli, Subba R.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 19, 11.05.2010, p. 8557-8562.

Research output: Contribution to journalArticle

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AU - Zhu, Fang

AU - Parthasarathy, R.

AU - Bai, Hua

AU - Woithe, Katharina

AU - Kaussmann, Martin

AU - Nauen, Ralf

AU - Harrison, Douglas A.

AU - Palli, Subba R.

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AB - Cytochrome P450-mediated detoxification is one of the most important mechanisms involved in insecticide resistance. However, the molecular basis of this mechanism and the physiological functions of P450s associated with insecticide resistance remain largely unknown. Here, we exploited the functional genomics and reverse genetic approaches to identify and characterize a P450 gene responsible for the majority of deltamethrin resistance observed in the QTC279 strain of Tribolium castaneum. We used recently completed whole-genome sequence of T. castaneum to prepare custom microarrays and identified a P450 gene, CYP6BQ9, which showed more than a 200-fold higher expression in the deltamethrin-resistant QTC279 strain when compared with its expression in the deltamethrin-susceptible Lab-S strain. Functional studies using both double-strand RNA (dsRNA)-mediated knockdown in the expression of CYP6BQ9 and transgenic expression of CYP6BQ9 in Drosophila melanogaster showed that CYP6BQ9 confers deltamethrin resistance. Furthermore, CYP6BQ9 enzyme expressed in baculovirus metabolizes deltamethrin to 4-hydroxy deltamethrin. Strikingly, we also found that unlike many P450 genes involved in insecticide resistance that were reported previously, CYP6BQ9 is predominantly expressed in the brain, a part of the central nervous system (CNS) containing voltage-gated sodium channels targeted by deltamethrin. Taken together, the current studies on the brain-specific insect P450 involved in delta-methrin resistance shed new light on the understanding of the molecular basis and evolution of insecticide resistance.

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