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.
