title: Risk assessment studies on succinate dehydrogenase inhibitors, the new weapons in the battle to control Septoria leaf blotch in wheat.
abstract: Chemical control of Septoria leaf blotch, caused by Mycosphaerella graminicola, is essential to ensure wheat yield and food security in most European countries. Mycosphaerella graminicola has developed resistance to several classes of fungicide and, with the efficacy of azoles gradually declining over time, new modes of action and/or improvements in host varietal resistance are urgently needed to ensure future sustainable disease control. Several new-generation carboxamide fungicides with broad-spectrum activity have recently been introduced into the cereal market. Carboxamides inhibit succinate dehydrogenase (Sdh) of the mitochondrial respiratory chain (complex II) but, because of their single-site specificity, these fungicides may be prone to resistance development. The objective of this study was to assess the risk of resistance development to different Sdh inhibitor (SDHI) fungicides in M. graminicola. UV mutagenesis was conducted to obtain a library of carboxin-resistant mutants. A range of SDHI resistance-conferring mutations was found in Sdh subunits B, C and D. Pathogenicity studies with a range of Sdh variants did not detect any fitness costs associated with these mutations. Most of the amino acid residues identified (e.g. B-S221P/T, B-H267F/L/N/Y, B-I269V and D-D129E/G/T) are directly involved in forming the cavity in which SDHI fungicides bind. Docking studies of SDHI fungicides in structural models of wild-type and mutated Sdh complexes also indicated which residues were important for the binding of different SDHI fungicides and showed a different binding for fluopyram. The predictive power of the model was also shown. Further diagnostic development, enabling the detection of resistant alleles at low frequencies, and cross-resistance studies will aid the implementation of anti-resistance strategies to prolong the cost-effectiveness and lifetime of SDHI fungicides.
authors.affiliation: Rothamsted Research, Plant Pathology and Microbiology Department, Harpenden, Hertfordshire AL5 2JQ, UK. bart.fraaije@rothamsted.ac.uk
authors.forename: Bart A
authors.initials: BA
authors.lastname: Fraaije
authors.forename: Carlos
authors.initials: C
authors.lastname: Bayon
authors.forename: Sarah
authors.initials: S
authors.lastname: Atkins
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Cools
authors.forename: John A
authors.initials: JA
authors.lastname: Lucas
authors.forename: Marco W
authors.initials: MW
authors.lastname: Fraaije
mesh_terms: D001203:Ascomycota / Q000187:drug effects / Q000472:pathogenicity*; D025141:Drug Resistance, Fungal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005659:Fungicides, Industrial / Q000494:pharmacology*; D010935:Plant Diseases / Q000517:prevention & control*; D018515:Plant Leaves / Q000382:microbiology*; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors*; D014908:Triticum / Q000382:microbiology*
chemical_list: D004791:Enzyme Inhibitors; D005659:Fungicides, Industrial; D013385:Succinate Dehydrogenase