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Published on: February 15, 2019
Fungal fludioxonil sensitivity is diminished by a constitutively active form of the group III histidine kinase
Kentaro Furukawa1, Anmoldeep Randhawa, Harsimran Kaur
1Department of Chemistry and Molecular Biology, University of Gothenburg, Box 462, 40530 Gothenburg, Sweden. kentaro.furukawa@cmb.gu.se
Abstract:
The fungicide fludioxonil is used to control plant-pathogenic fungi by causing improper activation of the Hog1-type MAPK. However, the appearance of fludioxonil resistant mutants, mostly caused by mutations in the group III histidine kinases, poses a serious problem. Moreover, such mutations cause also hyperosmotic sensitivity and the underlying mechanism has been elusive for a long time. Using Saccharomyces cerevisiae as an experimental host, we show that those phenotypes are conferred by a constitutively active form of the group III histidine kinase. Our results explain the different reasons for fludioxonil resistance conferred by its deletion and missense mutation.
Insights
Fludioxonil resistance in fungi, often due to mutations in histidine kinases, causes hyperosmotic sensitivity. Constitutively active histidine kinases explain these fungicide resistance and sensitivity phenotypes.
Area of Science:
- Biochemistry
- Molecular Biology
- Mycology
Background:
- Fludioxonil is a fungicide targeting plant-pathogenic fungi via Hog1-type MAPK pathway.
- Mutations in group III histidine kinases confer fludioxonil resistance but also cause hyperosmotic sensitivity.
- The mechanism linking these mutations to both phenotypes was previously unclear.
Purpose of the Study:
- To elucidate the mechanism behind fludioxonil resistance and hyperosmotic sensitivity in mutants.
- To investigate the role of constitutively active group III histidine kinases in conferring these phenotypes.
Main Methods:
- Utilized Saccharomyces cerevisiae as a model organism.
- Analyzed the effects of specific mutations in group III histidine kinases.
- Investigated the activation state of the histidine kinase and its downstream effects.
Main Results:
- Demonstrated that constitutively active group III histidine kinases confer both fludioxonil resistance and hyperosmotic sensitivity.
- Explained the distinct reasons for fludioxonil resistance arising from deletion versus missense mutations in histidine kinases.
- Provided mechanistic insight into the observed phenotypes.
Conclusions:
- Constitutively active group III histidine kinases are central to understanding fludioxonil resistance and associated hyperosmotic sensitivity.
- The study clarifies the molecular basis for differential resistance conferred by various mutation types.
- Findings contribute to understanding fungicide resistance mechanisms and fungal stress responses.
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