A small molecule species specifically inhibits Fusarium myosin I. (27th January 2015)

• Record Type: Journal Article
• Authors: Zhang, Chengqi; Chen, Yun; Yin, Yanni; Ji, Huan‐Hong; Shim, Won‐Bo; Hou, Yiping; Zhou, Mingguo; Li, Xiang‐dong; Ma, Zhonghua
• Is Part Of: Environmental microbiology. Volume 17:Number 8(2015:Aug.)
• Page Start: 2735
• Page End: 2746
• Publication Date: 2015-01-27
• Subjects: Microbial ecology -- Periodicals; Environmental Microbiology -- Periodicals; 579.17
• DOI: 10.1111/1462-2920.12711
• Languages: English
• ISSNs: 1462-2912

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p> <italic>F</italic> <italic>usarium</italic> head blight (FHB) caused by <italic>F</italic><italic>usarium graminearum</italic> 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 <italic>F</italic><italic>usarium</italic> 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 <italic>F</italic><italic>. graminearum</italic> (FgMyo1). FgMyo1 is essential for <italic>F</italic><italic>. graminearum</italic> growth. A point mutation S217L or E420K in FgMyo1 is responsible for <italic>F</italic><italic>. graminearum</italic> resistance to JS399‐19. In addition, transformation of <italic>F</italic><italic>. graminearum</italic> with the myosin I gene of <italic>M</italic><italic>agnaporthe grisea</italic>, 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<sup>S217L/E420K</sup>. 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.</p> </abstract>