A dispensable paralog of succinate dehydrogenase subunit C mediates standing resistance towards a subclass of SDHI fungicides in Zymoseptoria tritici

Autor: Stephanie Widdison, Regula Frey, Stefano F.F. Torriani, Rasmus Borup Hansen, Robert A. Dietrich, Grace Logan, Torsten Luksch, Helge Sierotzki, Gabriel Scalliet, Gert H. J. Kema, Stephane Bieri, Marie Salat, Diana Steinhauer, Andreas Mosbach, Dirk Balmer
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Artificial Gene Amplification and Extension
Biochemistry
Polymerase Chain Reaction
Geographical Locations
Mobile Genetic Elements
Genotype
Biology (General)
Energy-Producing Organelles
Fungicides
Genetics
0303 health sciences
Succinate dehydrogenase
030302 biochemistry & molecular biology
Fungal genetics
Agriculture
Genomics
Phenotype
Mitochondria
Fungicide
Europe
Succinate Dehydrogenase
Cellular Structures and Organelles
Agrochemicals
Research Article
Transposable element
medicine.medical_specialty
QH301-705.5
Protein subunit
Immunology
Paralogous Gene
Mycology
Biology
Bioenergetics
Research and Analysis Methods
Microbiology
03 medical and health sciences
Biointeractions and Plant Health
Genetic Elements
Ascomycota
Drug Resistance
Fungal
Virology
Molecular genetics
medicine
Life Science
Fungal Genetics
Molecular Biology Techniques
Gene
Molecular Biology
030304 developmental biology
Plant Diseases
Transposable Elements
Biology and Life Sciences
Cell Biology
RC581-607
Reverse genetics
Fungicides
Industrial
Genetic Loci
People and Places
biology.protein
Parasitology
Immunologic diseases. Allergy
Zdroj: PLoS Pathogens
PLoS Pathogens 15 (2019) 12
PLoS Pathogens, Vol 15, Iss 12, p e1007780 (2019)
PLoS Pathogens, 15(12)
ISSN: 1553-7366
DOI: 10.1101/616904
Popis: Succinate dehydrogenase inhibitor (SDHI) fungicides are widely used for the control of a broad range of fungal diseases. This has been the most rapidly expanding fungicide group in terms of new molecules discovered and introduced for agricultural use over the past fifteen years. A particular pattern of differential sensitivity (resistance) to the stretched heterocycle amide SDHIs (SHA-SDHIs), a subclass of chemically-related SDHIs, was observed in naïve Zymoseptoria tritici populations not previously exposed to these chemicals. Subclass-specific resistance was confirmed at the enzyme level but did not correlate with the genotypes of the succinate dehydrogenase (SDH) encoding genes. Mapping and characterization of the molecular mechanisms responsible for standing SHA-SDHI resistance in natural field isolates identified a gene paralog of SDHC, termed ZtSDHC3, which encodes for an alternative C subunit of succinate dehydrogenase, named alt-SDHC. Using reverse genetics, we showed that alt-SDHC associates with the three other SDH subunits, leading to a fully functional enzyme and that a unique Qp-site residue within the alt-SDHC protein confers SHA-SDHI resistance. Enzymatic assays, computational modelling and docking simulations for the two SQR enzymes (altC-SQR, WT_SQR) enabled us to describe enzyme-inhibitor interactions at an atomistic level and to propose rational explanations for differential potency and resistance across SHA-SDHIs. European Z. tritici populations displayed a presence (20–30%) / absence polymorphism of ZtSDHC3, as well as differences in ZtSDHC3 expression levels and splicing efficiency. These polymorphisms have a strong impact on SHA-SDHI resistance phenotypes. Characterization of the ZtSDHC3 promoter in European Z. tritici populations suggests that transposon insertions are associated with the strongest resistance phenotypes. These results establish that a dispensable paralogous gene determines SHA-SDHIs fungicide resistance in natural populations of Z. tritici. This study paves the way to an increased awareness of the role of fungicidal target paralogs in resistance to fungicides and demonstrates the paramount importance of population genomics in fungicide discovery.
Author summary Zymoseptoria tritici is the causal agent of Septoria tritici leaf blotch (STB) of wheat, the most devastating disease for cereal production in Europe. Multiple succinate dehydrogenase inhibitor (SDHI) fungicides have been developed and introduced for the control of STB. We report the discovery and detailed characterization of a paralog of the C subunit of the SDH enzyme conferring standing resistance towards the SHA-SDHIs, a particular chemical subclass of the SDHIs. The SDHC paralog is characterized by its presence/absence, expression and alternative splicing polymorphisms, which in turn influence resistance levels. The identified mechanisms exemplify the importance of population genomics for the discovery and rational design of the most adapted solutions.
Databáze: OpenAIRE
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