title: Hog1p activation by marasmic acid through inhibition of the histidine kinase Sln1p.
abstract: BACKGROUND
  The histidine kinase (HK) MoHik1p within the high-osmolarity glycerol (HOG) pathway is known to be the target of the fungicide fludioxonil. Treatment of the fungus with fludioxonil causes an uncontrolled hyperactivation of the pathway and cell death. In this study, we used a target-based in vivo test system with mutant strains of the rice blast fungus Magnaporthe oryzae to search for new fungicidal compounds having various target locations within the HOG pathway. Mutants with inactivated HOG signalling are resistant to fungicides having the target located in the HOG pathway.
  
  
  RESULTS
  The HK MoSln1p was identified as being involved in the new antifungal mode of action of marasmic acid, as single inactivation of the genes MoSLN1, MoSSK1, MoSSK2, MoPBS2 and MoHOG1 resulted in mutant strains resistant against the sesquiterpenoid, whereas the wild-type strain and the ΔMohik1 mutant were susceptible. Western blot analysis of phosphorylated MoHog1p confirmed the hypothesis that marasmic acid interferes with the HOG pathway, as a strong phosphorylation of MoHog1p was detectable after sesquiterpenoid treatment in the wild-type strain but not in the ΔMosln1 mutant.
  
  
  CONCLUSIONS
  This study provides evidence for marasmic acid activating the HOG pathway via the HK MoSln1p, and we propose that the sesquiterpenoid has a new mode of action in M. oryzae that differs from that of known HOG inhibitors, e.g. fludioxonil. © 2016 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
authors.affiliation: Institut für Biotechnologie und Wirkstoff-Forschung gGmbH (IBWF), Kaiserslautern, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Jacob
authors.affiliation: Institut für Biotechnologie und Wirkstoff-Forschung gGmbH (IBWF), Kaiserslautern, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schüffler
authors.affiliation: Institut für Biotechnologie und Wirkstoff-Forschung gGmbH (IBWF), Kaiserslautern, Germany.|Institut für Mikrobiologie und Weinforschung, Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thines
mesh_terms: D015153:Blotting, Western; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005659:Fungicides, Industrial / Q000494:pharmacology*; D005990:Glycerol / Q000378:metabolism; D000071677:Histidine Kinase / Q000037:antagonists & inhibitors*; D020082:Magnaporthe / Q000187:drug effects* / Q000235:genetics; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D012275:Oryza / Q000382:microbiology; D010935:Plant Diseases / Q000382:microbiology / Q000517:prevention & control; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes / Q000494:pharmacology
chemical_list: D005656:Fungal Proteins; D005659:Fungicides, Industrial; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C037486:marasmic acid; D000071677:Histidine Kinase; D005990:Glycerol
keywords: HOG pathway; Magnaporthe oryzae; hik1; histidine kinase; marasmic acid; osmoregulation; sesquiterpenoids; sln1