title: Sterol content analysis suggests altered eburicol 14alpha-demethylase (CYP51) activity in isolates of Mycosphaerella graminicola adapted to azole fungicides.
abstract: The recent decline in the effectiveness of some azole fungicides in controlling the wheat pathogen Mycosphaerella graminicola has been associated with mutations in the CYP51 gene encoding the azole target, the eburicol 14alpha-demethylase (CYP51), an essential enzyme of the ergosterol biosynthesis pathway. In this study, analysis of the sterol content of M. graminicola isolates carrying different variants of the CYP51 gene has revealed quantitative differences in sterol intermediates, particularly the CYP51 substrate eburicol. Together with CYP51 gene expression studies, these data suggest that mutations in the CYP51 gene impact on the activity of the CYP51 protein.
authors.affiliation: Department of Plant Pathology and Microbiology, Centre for Sustainable Pest and Disease Management, Rothamsted Research, Harpenden, Hertfordshire, UK.
authors.forename: Tim P
authors.initials: TP
authors.lastname: Bean
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Cools
authors.forename: John A
authors.initials: JA
authors.lastname: Lucas
authors.forename: Nathaniel D
authors.initials: ND
authors.lastname: Hawkins
authors.forename: Jane L
authors.initials: JL
authors.lastname: Ward
authors.forename: Michael W
authors.initials: MW
authors.lastname: Shaw
authors.forename: Bart A
authors.initials: BA
authors.lastname: Fraaije
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001203:Ascomycota / Q000737:chemistry* / Q000187:drug effects / Q000201:enzymology*; D001393:Azoles / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D025141:Drug Resistance, Fungal; D005656:Fungal Proteins / Q000378:metabolism*; D020869:Gene Expression Profiling; D007810:Lanosterol / Q000031:analogs & derivatives / Q000032:analysis; D058886:Sterol 14-Demethylase; D013261:Sterols / Q000032:analysis*; D014908:Triticum
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D005656:Fungal Proteins; D013261:Sterols; D007810:Lanosterol; C014520:ebericol; D003577:Cytochrome P-450 Enzyme System; D058886:Sterol 14-Demethylase