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

这个小型企业技术(STTR)项目的更广泛的影响/商业潜力是开发新的和变革性的杀菌策略，这些策略更有效、更环保、毒性更低，但仍然可以以合理和有竞争力的成本生产和获得。80%以上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的最有效和最广泛使用的策略。很大一部分作物杀菌剂市场包括两类杀菌剂：三唑类和白三烯类。这两类药物的使用量都越来越大，以克服正在形成的耐药性，而且这两种药物在高水平使用时都有已知的人类和动物毒性。用于治疗人类和动物急性真菌疾病(如曲霉病)的治疗性抗真菌药物出现耐药性，直接与过度使用最广泛使用的三唑类作物杀菌剂有关。因此，由于耐药性、环境影响、动物/人类毒性和成本导致的药效下降，对这些和其他化学杀菌剂的使用提出了挑战。研究和使用新的抗真菌药物氨基糖苷K20与三氮唑和白鲜菌素具有协同作用，以解决这些挑战，以及对这种转化策略的需求。这项STTRI期项目建议开发高产率和高纯度的氨基糖苷类杀菌剂K20的合成工艺，并使用标准棋盘分析方法测定每批K20与甲康唑或吡氯菌酯联合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的温室和田间试验。在表现出增效作用的组合中，有K20与甲康唑和吡虫菊酯混用。这些杀菌剂的广泛和大量使用与一些环境和人/动物健康问题有关。小麦、大麦和玉米的赤霉病病原菌--禾谷镰刀菌对小麦、大麦和玉米的赤霉病具有显著和一致的协同抑制活性。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。它提供了使用数量大大减少的杀菌剂进行作物保护的可能性，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上升趋势。

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.