A Rothamsted Research pipeline aims to speed fungicide discovery for Septoria tritici blotch by screening microbial compounds.
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Researchers aim to speed up the search for new antifungal compounds as wheat pathogens show reduced sensitivity to existing fungicides.
A new study from Rothamsted Research has set out a pipeline to accelerate the discovery of microbial compounds that could serve as leads for future fungicides.
The approach begins with a high-throughput in vitro bioassay to identify environmental bacterial isolates that inhibit Zymoseptoria tritici, the fungus responsible for Septoria tritici blotch. The researchers then combine this screening with genome mining, mutagenesis and analytical chemistry to identify the compounds behind the antifungal activity.
Septoria tritici blotch is one of the UK’s most important wheat diseases. Its causal pathogen, Z. tritici, has repeatedly evolved reduced sensitivity to major classes of commercial fungicides, making the search for new modes of control increasingly urgent.
The pipeline was developed as part of Rothamsted’s Growing Health Institute Strategic Programme and supported by UKRI through the Biotechnology and Biological Sciences Research Council (BBSRC), according to a press release.
Testing Bacterial Isolates Against Diverse Fungal Strains
In the study, the team screened a library of 534 environmental Pseudomonas isolates and found 52 that suppressed a standard Z. tritici strain. Selected promising isolates were then tested against a genetically diverse panel of 12 Z. triticiisolates collected from across Europe.
The results showed substantial variation in how strongly different fungal isolates were inhibited. This suggests that activity against a single reference strain may not provide a complete picture of a candidate’s potential. The findings support testing future antifungal leads against genetically diverse pathogen panels earlier in the discovery process, rather than assuming one strain can represent the wider pathogen population.
Identifying Known and Novel Antifungal Molecules
The researchers also began to uncover the biology behind the observed inhibition. Their analysis identified bacterial genes associated with the production of antifungal molecules, including the known antifungal compound 2,4-diacetylphloroglucinol (2,4-DAPG). In a proof-of-concept experiment, disrupting a key gene involved in 2,4-DAPG production caused the bacterial mutant to lose both 2,4-DAPG production and its visible ability to inhibit Z. tritici in the assay.
Importantly, the study also identified antagonistic isolates whose activity could not be readily explained by similarity to known reference gene clusters. This indicates that some strains may produce previously unknown antifungal molecules, giving researchers a practical way to prioritise the most promising candidates for further investigation.
“Zymoseptoria tritici remains a major challenge for wheat production, and new solutions are urgently needed for farmers,” Dr. George Lund, lead author of the study at Rothamsted Research, said. “What this pipeline gives us is a practical way to search for future fungicide leads from bacteria in a much more informed way. It also allows us to test candidates against genetically diverse Zymoseptoria isolates early in the process. That matters because activity seen against one strain may not always translate across the wider pathogen population, so this gives us a better way to decide which microbial metabolites are most worth pursuing.”
Scalable Approach Could Support Future Fungicide Research
While the work was conducted in vitro and does not yet demonstrate field performance, it establishes a scalable, cost-effective approach for discovering and prioritising candidate antifungal metabolites active against Z. tritici. In future studies, the same platform could also be used to assess whether promising molecules are effective against other fungal pathogens.
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