title: A small molecule species specifically inhibits Fusarium myosin I.
abstract: Fusarium head blight (FHB) caused by Fusarium graminearum is a devastating disease of cereal crops worldwide. Recently, a novel fungicide JS399-19 has been launched into the marketplace to manage FHB. It is compelling that JS399-19 shows highly inhibitory activity towards some Fusarium species, but not to other fungi, indicating that it is an environmentally compatible fungicide. To explore the mode of action of this species-specific compound, we conducted a whole-genome transcript profiling together with genetic and biochemical assays, and discovered that JS399-19 targets the myosin I of F. graminearum (FgMyo1). FgMyo1 is essential for F. graminearum growth. A point mutation S217L or E420K in FgMyo1 is responsible for F. graminearum resistance to JS399-19. In addition, transformation of F. graminearum with the myosin I gene of Magnaporthe grisea, the causal agent of rice blast, also led to JS399-19 resistance. JS399-19 strongly inhibits the ATPase activity of the wild-type FgMyo1, but not the mutated FgMyo1(S217L/E420K) . These results provide us a new insight into the design of species-specific antifungal compounds. Furthermore, our strategy can be applied to identify novel drug targets in various pathogenic organisms.
authors.affiliation: Institute of Biotechnology, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Chengqi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institute of Biotechnology, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Biotechnology, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Yanni
authors.initials: Y
authors.lastname: Yin
authors.affiliation: National Laboratory of Integrated Management of Insect Pests and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Huan-Hong
authors.initials: HH
authors.lastname: Ji
authors.affiliation: Department of Plant Pathology and Microbiology, Texas A&M University, College Station, TX, 77843-2132, USA.
authors.forename: Won-Bo
authors.initials: WB
authors.lastname: Shim
authors.affiliation: Department of Plant Pathology, Nanjing Agricultural University, Nanjing, 210095, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of Plant Pathology, Nanjing Agricultural University, Nanjing, 210095, China.
authors.forename: Mingguo
authors.initials: M
authors.lastname: Zhou
authors.affiliation: National Laboratory of Integrated Management of Insect Pests and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Li
authors.affiliation: Institute of Biotechnology, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Ma
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000596:Amino Acids / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D002523:Edible Grain / Q000382:microbiology; D005659:Fungicides, Industrial / Q000494:pharmacology*; D005670:Fusarium / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D020869:Gene Expression Profiling; D020082:Magnaporthe / Q000235:genetics; D024461:Myosin Type I / Q000037:antagonists & inhibitors* / Q000235:genetics; D010666:Phenylpropionates / Q000494:pharmacology*; D010935:Plant Diseases / Q000382:microbiology
chemical_list: C540078:2-cyano-3-amino-3-phenylacrylic acid; D000596:Amino Acids; D000935:Antifungal Agents; D005659:Fungicides, Industrial; D010666:Phenylpropionates; D000251:Adenosine Triphosphatases; D024461:Myosin Type I