Award details

Impact of mutations in the target-encoding CYP51 gene in Mycosphaerella graminicola populations developing resistance to triazole fungicides

Reference	BBS/E/C/00004906
Principal Investigator / Supervisor	Professor John Lucas
Co-Investigators / Co-Supervisors	Dr Bart Fraaije
Institution	Rothamsted Research
Department	Rothamsted Research Department
Funding type	Research
Value (£)	49,362
Status	Completed
Type	Institute Project
Start date	01/12/2007
End date	01/05/2011
Duration	41 months

Abstract

Several mechanisms are known to contribute to resistance to azoles. These include changes in the target site protein, as well as participation of other proteins, known as transporters, that are able to pump the fungicide out of the fungus. Therefore, to understand how changes in the target protein may affect azole sensitivity, the altered forms of the protein must be expressed and studied in isolation. The proposed project aims to determine the effect on sensitivity of mutations in the azole target that is a cytochrome P450 called CYP51 involved in sterol 14?-demethylation. The research will assess how such mutations affect interactions between the fungicide and the protein, as well as the activity of the enzyme itself, using several approaches. The mutant proteins will be expressed in another fungus, the yeast Saccharomyces cerevisiae, to see how sensitivity to different azoles is affected, and to make pure samples of the protein to measure enzyme activity, altered properties and inhibition. Many of the changes detected by DNA sequencing of the azole target gene have not been seen in clinical resistance and therefore require characterisation. Indeed, few of the mutations associated with resistance have been characterised at the level of purified protein even in the clinical setting. In particular the project will concentrate on a variety of mutations that have occurred quite recently in M. graminicola populations exposed to azole fungicides. We also intend to introduce further changes to the protein by targeted mutation to assess their effects on sensitivity and protein function.

Summary

unavailable

Committee	Closed Committee - Agri-food (AF)
Research Topics	Crop Science, Microbiology, Plant Science
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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