STTR Phase I: New Synergistic Biofungicides - Novel Aminoglycoside and Azole/Strobulin Combinations

这个小型企业技术项目的更广泛的影响/商业潜力是发展新的和变革性的杀真菌战略，这些战略更有效、更环保、毒性更小，但仍然以合理和有竞争力的成本生产和提供。超过80%的农作物和草坪病害是由真菌感染引起的。直接使用化学杀菌剂仍然是控制这些疾病最有效和广泛使用的策略。作物杀菌剂市场的很大一部分包括两类杀菌剂：三唑类和特罗布林类。这两类药物的使用量越来越大，以克服正在形成的耐药性，并且在高剂量使用时，两者都具有已知的人类和动物毒性。对用于治疗急性人类和动物真菌疾病（如曲霉病）的治疗性抗真菌药物的新耐药性与过度使用最广泛使用的三唑类作物杀菌剂直接相关。因此，由于耐药性、环境影响、动物/人类毒性和成本等因素导致的有效性下降，对这些化学杀菌剂和其他化学杀菌剂的使用提出了挑战。本提案中描述的新型抗真菌氨基糖苷K20与三唑和strobulins协同作用的研究和使用解决了这些挑战，以及对这种变革策略的需求。本STTR一期项目拟制定高产、高纯度氨基糖苷类杀菌剂K20的合成方案，并采用标准棋盘分析法测定每批K20与甲康唑或嘧菌酯联合使用时的分数抑制浓度指数（FICI）。此外，该计划还将进行k20 -杀菌剂组合防治小麦赤霉病（FHB）的温室和田间试验。K20与甲康唑和吡咯菌酯混合使用具有协同作用。这些杀菌剂的广泛和大量使用与一些环境和人类/动物健康问题有关。对小麦、大麦和玉米赤霉病（Fusarium head blight， FHB）的病原菌禾谷镰刀菌（Fusarium graminearum）具有显著而一致的协同抑制作用。K20与这些广泛使用的杀菌剂之间的协同作用具有广泛而重要的意义。它提供了在作物保护中使用更少量杀菌剂的可能性，这将抵消全球真菌耐药性的增加，并扭转人类和动物健康问题的增加。

The broader impact/commercial potential of this Small Business Technology (STTR) project is the development of new and transformative fungicidal strategies that are more effective, ecofriendly, less toxic, but still produced and available at reasonable and competitive cost. More than 80% of crop and turf diseases are due to fungal infections. Direct application of chemical fungicides continues to be the most effective and widely used strategy to control these diseases. A large fraction of the crop fungicide market includes two fungicide classes: The triazoles and strobulins. Both classes are used in increasingly larger amounts to overcome developing resistance, and both have known human and animal toxicities when used at high levels. Emerging resistance to therapeutic antifungals for treatment of acute human and animal fungal diseases (e.g. aspergillosis) has been directly linked to the overuse of the most widely used triazole crop fungicides. Therefore, declining effectiveness due to resistance, environmental impacts, animal/human toxicity, and costs challenge the use of these and other chemical fungicides. The research and use of the novel antifungal aminoglycoside K20 that acts synergistically with triazoles and strobulins as described in this proposal address these challenges, and the need for such transformative strategies.This STTR Phase I project proposes to develop the synthetic protocol for production of aminoglycoside fungicide K20 in high yield and purity, and determine the fractional inhibitory concentration index (FICI) for each batch of K20 in combination with metconazole or pyrachlostrobin using standard checkerboard analyses. In addition, the plan is to conduct greenhouse and field tests of K20-fungicide combinations against Fusarium head blight (FHB) disease of wheat. Among the combinations showing synergy are K20 mixed with metconazole and pyrachlostrobin. The widespread and heavy use of these fungicides has been linked to a number of environmental and human/animal health issues. Striking and consistent synergistic inhibitory activities are observed with the crop pathogen Fusarium graminearum - the causative agent of Fusarium head blight (FHB) of wheat, barley and corn. The synergism between K20 and these widely used fungicides has broad and important implications. It offers the possibility of using dramatically smaller amounts of fungicides for crop protection, which will counter the increases in global fungal resistance, and reverse the rise in human and animal health problems.