title: 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.
authors.affiliation: Department of Molecular Phytopathology and Genetics, Biocenter Klein Flottbek, University of Hamburg, Ohnhorststrasse 18, D-22609 Hamburg, Germany.
authors.forename: Mayada
authors.initials: M
authors.lastname: Woriedh
authors.forename: Ilona
authors.initials: I
authors.lastname: Hauber
authors.forename: Ana Lilia
authors.initials: AL
authors.lastname: Martinez-Rocha
authors.forename: Christian
authors.initials: C
authors.lastname: Voigt
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Maier
authors.forename: Marcus
authors.initials: M
authors.lastname: Schröder
authors.forename: Chris
authors.initials: C
authors.lastname: Meier
authors.forename: Joachim
authors.initials: J
authors.lastname: Hauber
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Schäfer
mesh_terms: D003001:Cloning, Molecular; D005670:Fusarium / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D005800:Genes, Fungal / Q000235:genetics; D017343:Genes, Plant / Q000235:genetics; D018525:Germination / Q000187:drug effects; D006835:Hydrazones / Q000494:pharmacology*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010448:Peptide Initiation Factors / Q000187:drug effects / Q000378:metabolism; D010935:Plant Diseases / Q000382:microbiology*; D016601:RNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013172:Spores, Fungal / Q000187:drug effects / Q000502:physiology; D014908:Triticum / Q000201:enzymology / Q000235:genetics / Q000382:microbiology*; D003313:Zea mays / Q000201:enzymology / Q000235:genetics / Q000382:microbiology*; D000097574:Eukaryotic Translation Initiation Factor 5A; D000813:Anilides; D006146:Guanidines
chemical_list: D006835:Hydrazones; D000587:Oxidoreductases Acting on CH-NH Group Donors; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A; C097256:semapimod; D000813:Anilides; D006146:Guanidines; C063507:deoxyhypusine synthase