Insecticide detoxification indicator strains as tools for enhancing chemical discovery screens
Version of Record online: 16 JUN 2011
Copyright © 2011 Society of Chemical Industry
Pest Management Science
Volume 68, Issue 1, pages 38–48, January 2012
How to Cite
Shah, S., Yarrow, C., Dunning, R., Cheek, B., Vass, S., Windass, J. and Hadfield, S. (2012), Insecticide detoxification indicator strains as tools for enhancing chemical discovery screens. Pest. Manag. Sci., 68: 38–48. doi: 10.1002/ps.2218
- Issue online: 20 DEC 2011
- Version of Record online: 16 JUN 2011
- Manuscript Accepted: 27 APR 2011
- Manuscript Revised: 23 APR 2011
- Manuscript Received: 21 SEP 2010
- xenobiotic detoxification;
BACKGROUND: Insecticide discovery screens carried out on whole organisms screen for potency resulting from chemical activity at the target site. However, many potentially insecticidal compounds are naturally detoxified in vivo and do not make it to the target site. It is hypothesised that insect strains with their xenobiotic detoxification machinery compromised could be used to identify such compounds that normally fail to show up in screens; these compounds could then be more rationally designed to increase their bioavailability. This strategy was tested with transgenic Drosophila lines with altered expression of Cyp6g1 and Dhr96.
RESULTS: It was observed that Cyp6g1 knockdown transgenic lines have increased susceptibility to the test compound imidacloprid, while Dhr96 knockdown transgenic lines are resistant. Evidence was found for a systemic response to xenobiotic exposure, uncovered by piperonyl butoxide treatment and by gene expression profiling. Sex-specific gene expression regulated by DHR96 was also observed.
CONCLUSION: The results confirm that this approach to chemical discovery could identify compounds that escape traditional screens. The complexity of the system means that a panel of single and multiple gene knockdown transgenic lines may be required. Copyright © 2011 Society of Chemical Industry