A Eukaryotic Molecular Target Candidate of Roxithromycin: Fungal Differentiation as a Sensitive Drug Target Analysis System

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  • ISHII Akira
    Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science
  • KUMASAKA Mayu
    Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science
  • NAGASHIMA Yuka
    Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science
  • NAKAJIMA Yuichi
    Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science
  • KURAMOCHI Kouji
    Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science
  • SUGAWARA Fumio
    Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science
  • NARUKAWA Megumi
    Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science
  • KAMAKURA Takashi
    Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science

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Roxithromycin (RXM), active against prokaryotes, has beneficial side effects such as anti-cancer activities on mammalian cells, but the mechanisms underlying these effects remain unclear. We found that RXM inhibited the cellular differentiation of the rice blast fungus Magnaporthe oryzae. Hence, we screened the targets of RXM by the T7 phage display method with fungal genomic DNA, and identified MoCDC27 (M. oryzae Cell Division Cycle 27) as a candidate. We generated mocdc27 knockdown mutants that the appressoria formation was less affected by RXM. A complemented mutant restored sensitivity against RXM to the level of the wild type. These results suggest that MoCDC27 was involved in the inhibition of appressorium formation by RXM, and that the complex of RXM-MoCDC27 affected another molecule involved in appressorium formation. The T7 phage display method with fungal genomic DNA can be a useful tool in the quest for drug target.

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