Preventing Fusarium Head Blight of Wheat and Cob Rot of Maize by Inhibition of Fungal Deoxyhypusine Synthase

Abstract

Upon posttranslational activation, the eukaryotic initiation factor-5A (eIF-5A) transports a subset of mRNAs out of the nucleus to the ribosomes for translation. Activation of the protein is an evolutionary highly conserved process that is unique to eIF-5A, the conversion of a lysine to a hypusine. Instrumental for the synthesis of hypusine is the first of two enzymatic reactions mediated by deoxyhypusine synthase (DHS). We show that DHS of wheat and the pathogenic fungus Fusarium graminearum, which causes one of the most destructive crop diseases worldwide, are transcriptionally upregulated during their pathogenic interaction. Although DHS of wheat, fungus, and human can be equally inhibited by the inhibitor CNI-1493 in vitro, application during infection of wheat and maize flowers results in strong inhibition of the pathogen without interference with kernel development. Our studies provide a novel strategy to selectively inhibit fungal growth without affecting plant growth. We identified fungal DHS as a target for the development of new inhibitors, for which CNI-1493 may serve as a lead substance.