REVEALING THE MECHANISMS OF NICOTINAMIDE TOXICITY IN FUNGAL PLANT PATHOGENS

Managing plant diseases caused by fungi is an issue of great importance; one of the obstacles in doing so is in the frequent acquisition of pesticide resistance. Novel approaches in pesticide development aim to target several cellular pathways in fungi and thus reducing the chance of resistance acquisition due to a single mutation in a single gene. Nicotinamide is a common metabolite in the cell that is involved in metabolism and energy production. Recent data indicate that if supplied in access nicotinamide is a natural histone deacetylase inhibitor. We found that increasing the amounts of nicotinamide in several ways is toxic to fungal plant pathogens and can mitigate plant disease. By performing RNA seq analysis of fungi exposed to nicotinamide and its derivative nicotinaldehyde we found that these agents target both the chromatin and the mitochondria. High-throughput screens performed using the yeast deletion collection confirmed that these two very different cellular modules are the targets of nicotinamide and nicotinaldehyde. We will discuss how revealing the mode of toxicity of the nicotinamide pathway can be utilized to develop novel antifungal strategies.