Identification and characterization of a dual-acting antinematodal agent against the pinewood nematode, Bursaphelenchus xylophilus

Wan Suk Oh, Pan Young Jeong, Hyoe Jin Joo, Jeong Eui Lee, Yil Seong Moon, Hyang Mi Cheon, Jung Ho Kim, Yong Uk Lee, Yhong Hee Shim, Young Ki Paik

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10 Citations (Scopus)

Abstract

The pinewood nematode (PWN), Bursaphelenchus xylophilus, is a mycophagous and phytophagous pathogen responsible for the current widespread epidemic of the pine wilt disease, which has become a major threat to pine forests throughout the world. Despite the availability of several preventive trunk-injection agents, no therapeutic trunk-injection agent for eradication of PWN currently exists. In the characterization of basic physiological properties of B. xylophilus YB-1 isolates, we established a high-throughput screening (HTS) method that identifies potential hits within approximately 7 h. Using this HTS method, we screened 206 compounds with known activities, mostly antifungal, for antinematodal activities and identified HWY-4213 (1-n-undecyl-2-[2-fluorphenyl] methyl-3,4-dihydro-6,7-dimethoxy-isoquinolinium chloride), a highly water-soluble protoberberine derivative, as a potent nematicidal and antifungal agent. When tested on 4 year-old pinewood seedlings that were infected with YB-1 isolates, HWY-4213 exhibited a potent therapeutic nematicidal activity. Further tests of screening 39 Caenorhabditis elegans mutants deficient in channel proteins and B. xylophilus sensitivity to Ca2+ channel blockers suggested that HWY-4213 targets the calcium channel proteins. Our study marks a technical breakthrough by developing a novel HTS method that leads to the discovery HWY-4213 as a dual-acting antinematodal and antifungal compound.

Original languageEnglish
Article numbere7593
JournalPloS one
Volume4
Issue number11
DOIs
Publication statusPublished - 2009 Nov 11

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Oh, W. S., Jeong, P. Y., Joo, H. J., Lee, J. E., Moon, Y. S., Cheon, H. M., Kim, J. H., Lee, Y. U., Shim, Y. H., & Paik, Y. K. (2009). Identification and characterization of a dual-acting antinematodal agent against the pinewood nematode, Bursaphelenchus xylophilus. PloS one, 4(11), [e7593]. https://doi.org/10.1371/journal.pone.0007593