Abstract
Zymoseptoria tritici causes septoria tritici blotch (STB), the predominant fungal disease in wheat in Denmark and Sweden. Disease control is highly reliant on fungicides in the group of demethylation inhibitors (DMI). The use of DMIs has increased steadily since their introduction in the 1970s. Epoxiconazole and prothioconazole were the most widely used active ingredients in the last ten years. The goal of this investigation was to survey the resistance development of Z. tritici towards these two compounds. In total, EC50 values were determined for 3472 Z. tritici isolates from 2012 to 2019. Also, the field performance of the most used DMI compounds was tested in field trials. EC50 values of epoxiconazole and prothioconazole increased in the testing period. A significant shift was observed for epoxiconazole in 2016 and again 2018 with average EC50 values >1 ppm in Denmark. In Sweden, average EC50 values for epoxiconazole reached 1 ppm in 2017. The sensitivity towards prothioconazole remained stable at a high level. Following the decline in sensitivity in vitro, field efficacies of epoxiconazole and prothioconazole decreased from 80 - 90% to 30 - 40% in Denmark and Sweden. Currently, the Danish and Swedish Z. tritici populations are highly adapted to epoxiconazole and prothioconazole. At the same time, a recovery in the sensitivity of tebuconazole and metconazole is observed. Our studies reinforce the view that the principles of anti-resistance management should be applied upon the launch of a new active ingredient to prolong the effective life of both the old and new products.
This is a preview of subscription content,
to check access.




References
Abbott, W. S. (1925). A method of computing the effectiveness of an insecticide. Journal of Economical Entomology, 18, 265–267.
Anonymous (2019). Afrapportering fra arbejdsgruppen vedr. azolresistens. https://www.ft.dk/samling/20181/almdel/MOF/bilag/407/2016336.pdf. Accessed 15 Dec 2019.
Blake, J. J., Gosling, P., Fraaije, B. A., Burnett, F. J., Knight, S. M., Kildea, S., & Paveley, N. D. (2018). Changes in field dose-response curves for demethylation inhibitor (DMI) and quinone outside inhibitor (QoI) fungicides against Zymoseptoria tritici, related to laboratory sensitivity phenotyping and genotyping assays. Pest Management Science, 74, 302–313.
Brown, J. K. M., Chartrain, L., Lasserre-Zuber, P., & Saintenac, C. (2015). Genetics of resistance to Zymoseptoria tritici and applications to wheat breeding. Fungal Genetic Biology, 79, 33–41. https://doi.org/10.1016/j.fgb.2015.04.017.
Cools, H. J., & Fraaije, B. A. (2013). Update on mechanisms of azole resistance in Mycosphaerella graminicola and implications for future control. Pest Management Science, 69, 150–155.
Cools, H. J., Mullins, J. G. L., Fraaije, B. A., Parker, J. E., Kelly, D. E., Lucas, J. A., & Kelly, S. L. (2011). Impact of recently emerged sterol 14 alpha-demethylase (CYP51) variants of Mycosphaerella graminicola on azole fungicide sensitivity. Applied and Environmental Microbiology, 77, 3830–3837.
Cools, H. J., Bayon, C., Atkins, S., Lucas, J. A., & Fraaije, B. A. (2012). Overexpression of the sterol 14 alpha-demethylase gene (MgCYP51) in Mycosphaerella graminicola isolates confers a novel azole fungicide sensitivity phenotype. Pest Management Science, 68, 1034–1040.
Dooley, H., Shaw, M. W., Spink, J., & Kildea, S. (2016a). Effect of azole fungicide mixtures, alternations and dose on azole sensitivity in the wheat pathogen Zymoseptoria tritici. Plant Pathology, 65, 124–136.
Dooley, H., Shaw, M. W., Spink, J., & Kildea, S. (2016b). The effect of succinate dehydrogenase inhibitor/azole mixtures on selection of Zymoseptoria tritici isolates with reduced sensitivity. Pest Management Science, 72, 1150–1159.
Dooley, H., Shaw, M. W., Mehenni-Ciz, J., Spink, J., & Kildea, S. (2016c). Detection of Zymoseptoria tritici SDHI-insensitive field isolates carrying the SdhC-H152R and SdhD-R47W substitutions. Pest Management Science, 72, 2203–2207.
Eyal, Z. (1999). The septoria tritici and stagonospora nodorum blotch diseases of wheat. European Journal of Plant Pathology, 105, 629–641.
Eyal, Z., Scharen, A. L., Prescott, J. M., & Van Ginkel, M. (1987). The septoria diseases of wheat: Concepts and methods of disease management. CIMMYT.
Garnault, M., Dupais, C., Leroux, P., Couleaud, G., Carpentier, F., David, O., & Walker, A. S. (2019). Spatiotemporal dynamics of fungicide resistance in the wheat pathogen Zymoseptoria Tritici in France. Pest Management Science, 75, 7–1807. https://doi.org/10.1002/ps.5360.
Goodwin, S. B. (2018). Diseases affecting wheat: Septoria tritici blotch. In O. Richard (Ed.), Integrated disease management of wheat and barley. Cambridge: Burleigh Dodds Science Publishing Limited.
Hawkins, N. J., & Fraaije, B. A. (2018). Fitness penalties in the evolution of fungicide resistance. Annual Review of Phytopathology, 56, 339–360.
Hawkins, N. J., Bass, C., Dixon, A., & Neve, P. (2019). The evolutionary origins of pesticide resistance. Biological Reviews, 94, 135–155.
Heick, T. M., Justesen, A. F., & Jorgensen, L. N. (2017a). Anti-resistance strategies for fungicides against wheat pathogen Zymoseptoria tritici with focus on DMI fungicides. Crop Protection, 99, 108–117.
Heick, T. M., Justesen, A. F., & Jorgensen, L. N. (2017b). Resistance of wheat pathogen Zymoseptoria tritici to DMI and QoI fungicides in the Nordic-Baltic region - a status. European Journal of Plant Pathology, 149, 669–682.
Huf, A., Rehfus, A., Lorenz, K. H., Bryson, R., Voegele, R. T., & Stammler, G. (2018). Proposal for a new nomenclature for CYP51 haplotypes in Zymoseptoria tritici and analysis of their distribution in Europe. Plant Pathology, 67, 1706–1712.
Jorgensen, L. N., Hovmoller, M. S., Hansen, J. G., Lassen, P., Clark, B., Bayles, R., Rodemann, B., Flath, K., Jahn, M., Goral, T., Czembor, J., Cheyron, P., Maumene, C., De Pope, C., Ban, R., Nielsen, G. C., & Berg, G. (2014). IPM strategies and their dilemmas including an introduction to www.eurowheat.org. Journal of Integrative Agriculture, 13, 265–281.
Jørgensen, L.N., Heick, T.M., Matzen, N., Madsen, H.P., Kristjansen, H.S., Kirkegaard, S., & Almskou-Dahlgaard, A. (2017). Disease control in cereals. In: Applied crop protection 2017, Aarhus University, DCA rapport Markbrug, 117, 16–52.
Jørgensen, L. N., Oliver, R. P., & Heick, T. M. (2018). Occurrence and avoidance of fungicide resistance in cereal diseases. In R. P. Oliver (Ed.), Integrated disease management of wheat and barley (pp. 235–259). Cambridge: Burleigh Dodds Science Publishing Limited.
Jorgensen, L. N., van den Bosch, F., Oliver, R. P., Heick, T. M., & Paveley, N. D. (2018a). Targeting fungicide inputs according to need. Annual Review of Phytopathology, 55, 181–203.
Jorgensen, L. N., Matzen, N., Hansen, J. G., Semaskiene, R., Korbas, M., Danielewicz, J., Glazek, M., Maumene, C., Rodemann, B., Weigand, S., Hess, M., Blake, J., Clark, B., Kildea, S., Batailles, C., Ban, R., Havis, N., & Treikale, O. (2018b). Four azoles’ profile in the control of Septoria, yellow rust and brown rust in wheat across Europe. Crop Protection, 105, 16–27.
Jørgensen, L.N., Matzen, N., Havis, N., Holdgate, S., Clark, B., Blake, J., Glazek, M., Korbas, M., Danielewicz, J., Maumene, C., Rodemann, B., Weigand, S., Kildea, S., Bataille, C., Brauna-Morževska, E., Gulbis, K., Ban, R., & Berg, G. (2020). Efficacy of common azoles and mefentrifluconazole against septoria, brown rust and yellow rust in wheat across Europe. In: Deising, HB., Fraaije, B., Mehl, A., Oerke, EC., Sierotzki, H., Stammler, G (Eds), "Modern Fungicides and Antifungal Compounds", Vol. IX pxx. © 2019 Deutsche. Phytomedizinische Gesellschaft, Braunschweig.
Kildea, S., Mehenni-Ciz, J., Spink, J., & O‘Sullivan E. (2015). Changes in the frequency of Irish Mycosphaerella graminicola CYP51 variants 2006-2011. In H. W. Dehne, H. B. Deising, B. Fraaije, U. Gisi, D. Hermann, A. Mehl, E. C. Oerke, P. E. Russell, G. Stammler, K. H. Kuck, & H. Lyr (Eds.), Modern fungicides and antifungal compounds VII (pp. 143–144). Braunschweig: DPG Spectrum Phytomedizin.
Kildea, S., Marten-Heick, T., Grant, J., Mehenni-Ciz, J., & Dooley, H. (2019). A combination of target-site alterations, overexpression and enhanced efflux activity contribute to reduced azole sensitivity present in the Irish Zymoseptoria tritici population. European Journal of Plant Pathology, 154, 529–540. https://doi.org/10.1007/s10658-019-01676-4.
Leroux, P., Albertini, C., Gautier, A., Gredt, M., & Walker, A. S. (2007). Mutations in the CYP51 gene correlated with changes in sensitivity to sterol 14 alpha-demethylation inhibitors in field isolates of Mycosphaerelia graminicola. Pest Management Science, 63, 688–698.
Mäe, A., Fillinger, S., Sooväli, P., & Heick, T. M. (2020). Fungicide sensitivity shifting of Zymoseptoria tritici in the Finnish-Baltic region and a novel insertion in the MFS1 promoter. Frontiers in Plant Science, 11, 385. https://doi.org/10.3389/fpls.2020.00385.
McDonald, M. C., Renkin, M., Spackman, M., Orchard, B., Croll, D., Solomon, C. P. S., & Milgate, A. (2019). Rapid parallel evolution of Azole fungicide resistance in Australian populations of the wheat pathogen Zymoseptoria tritici. Applied and Environmental Microbiology, 85, 85. https://doi.org/10.1128/AEM.01908-18.
O'Driscoll, A., Kildea, S., Doohan, F., Spink, J., & Mullins, E. (2014). The wheat-Septoria conflict: a new front opening up? Trends in Plant Science, 19, 602–610.
Omrane, S., Audeon, C., Ignace, A., Duplaix, C., Aouini, L., Kema, G., Walker, A. S., & Fillinger, S. (2017). Plasticity of the MFS1 promoter leads to multidrug resistance in the wheat pathogen Zymoseptoria tritici. Msphere, 2. https://doi.org/10.1128/mSphere.00393-17.
Owen, W. J., Yao, C. L., Myung, K., Kemmitt, G., Leader, A., Meyer, K. G., Bowling, A. J., Slanec, T., & Kramer, V. J. (2017). Biological characterization of fenpicoxamid, a new fungicide with utility in cereals and other crops. Pest Management Science, 73, 2005–2016.
Price, C. L., Parker, J. E., Warrilow, A. G. S., Kelly, D. E., & Kelly, S. L. (2015). Azole fungicides-understanding resistance mechanisms in agricultural fungal pathogens. Pest Management Science, 71, 1054–1058.
Rehfus, A., Strobel, D., Bryson, R., & Stammler, G. (2018). Mutations in sdh genes in field isolates of Zymoseptoria tritici and impact on the sensitivity to various succinate dehydrogenase inhibitors. Plant Pathology, 67, 175–180.
Savary, S., Willocquet, L., Pethybridge, S. J., Esker, P., McRoberts, N., & Nelson, A. (2019). The global burden of pathogens and pests on major food crops. Nature Ecology and Evolution, 3, 430–439. https://doi.org/10.1038/s41559-018-0793-y.
Sierotzki, H., & Scalliet, G. (2013). A review of current knowledge of resistance aspects for the next-generation succinate dehydrogenase inhibitor fungicides. Phytopathology, 103(9), 880–887.
Stammler, G., & Semar, M. (2011). Sensitivity of Mycosphaerella graminicola (Anamorph: Septoria tritici) to DMI fungicides across Europe and impact on field performance. Bulletin OEPP/EPPO Bulletin, 41(2), 149–155. https://doi.org/10.1111/j.1365-2338.2011.02454.x.
Suemoto, H., Matsuzaki, Y., & Iwahashi, F. (2019). Metyltetraprole, a novel putative complex III inhibitor, targets known QoI-resistant strains of Zymoseptoria tritici and Pyrenophora teres. Pest Management Science, 75(4), 1181–1189.
Sykes, E. M., Sackett, K. E., Severns, P. M., & Mundt, C. C. (2018). Sensitivity variation and cross-resistance of Zymoseptoria tritici to azole fungicides in North America. European Journal of Plant Pathology, 151, 269–274.
Tesh, S. A., Tesh, J. M., Fegert, I., Buesen, R., Schneider, S., Mentzel, T., van Ravenzwaay, B., & Stinchcombe, S. (2019). Innovative selection approach for a new antifungal agent mefentrifluconazole (Revysol®) and the impact upon its toxicity profile. Regulatory Toxicology and Pharmacology, 106, 152–168.
Thomas, M. R., Cook, R. J., & King, J. E. (1989). Factors affecting development of Septoria tritici in winter wheat and its effect on yield. Plant Pathology, 38, 246–257.
Vagndorf, N., Heick, T. M., Justesen, A. F., Andersen, J. R., Jahoor, A., Jorgensen, L. N., & Orabi, J. (2018). Population structure and frequency differences of CYP51 mutations in Zymoseptoria tritici populations in the Nordic and Baltic regions. European Journal of Plant Pathology, 152, 327–341.
van den Bosch, F., Oliver, R., van den Berg, F., & Paveley, N. (2014a). Governing principles can guide fungicide-resistance management tactics. Annual Review of Phytopathology, 52, 175–195.
van den Bosch, F., Paveley, N., van den Berg, F., Hobbelen, P., & Oliver, R. (2014b). Mixtures as a fungicide resistance management tactic. Plant Pathology, 104(12), 1264–1273.
Wieczorek, T. M., Berg, G., Semaskiene, R., Mehl, A., Sierotzki, H., Stammler, G., Justesen, A. F., & Jorgensen, L. N. (2015). Impact of DMI and SDHI fungicides on disease control and CYP51 mutations in populations of Zymoseptoria tritici from northern Europe. European Journal of Plant Pathology, 143, 861–871.
Yamashita, M., & Fraaije, B. (2018). Non-target site SDHI resistance is present as standing genetic variation in field populations of Zymoseptoria tritici. Pest Management Science, 74, 672–681.
Yang, N. N., McDonald, M. C., Solomon, P. S., & Milgate, A. W. (2018). Genetic mapping of Stb19, a new resistance gene to Zymoseptoria tritici in wheat. Theoretical and Applied Genetics, 131, 2765–2773.
Acknowledgments
The authors would like to thank Birgitte Boyer Frederiksen and Hanne-Birgitte Christensen for the engagement in the lab. Furthermore, gratitude to Gunilla Berg and the team from Jordbruksverket for providing leaf samples from Sweden. The included data from field trials were partly financed by the industry (BASF SE, Bayer CropScience, and Syngenta).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no conflicts of interest.
Human and animal studies
This research contained within did not involve human participants or animals.
Rights and permissions
About this article
Cite this article
Heick, T.M., Matzen, N. & Jørgensen, L.N. Reduced field efficacy and sensitivity of demethylation inhibitors in the Danish and Swedish Zymoseptoria tritici populations. Eur J Plant Pathol 157, 625–636 (2020). https://doi.org/10.1007/s10658-020-02029-2
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10658-020-02029-2