Journal
PARASITOLOGY
Volume 149, Issue 6, Pages 765-773Publisher
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S0031182022000191
Keywords
Angiostrongyliasis; anthelmintics; drug discovery; emerging infectious disease; Hawaiian fungi; motility assay; nematode; parasite; rat lungworm disease; wMicroTracker
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Funding
- National Institutes of Health (NIH)
- National Institute of General Medical Sciences (NIGMS)
- IDeA Networks of Biomedical Research Excellence (INBRE) [P20GM10346-18S1]
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This study developed a high-throughput screening method for parasitic nematodes using the wMicroTracker system, and validated its effectiveness in testing natural products against Angiostrongylus cantonensis. Screening of extracts from Hawaiian fungi led to the discovery of two previously unknown compounds with anthelmintic properties. The study also highlighted the value of A. cantonensis and Hawaiian fungi in the search for new anthelmintics.
Parasitic nematodes devastate human and animal health. The limited number of anthelmintics available is concerning, especially because of increasing drug resistance. Anthelmintics are commonly derived from natural products, e.g. fungi and plants. This investigation aimed to develop a high-throughput whole organism screening method based on a motility assay using the wMicroTracker system. Anthelmintic activity of extracts from Hawaiian fungi was screened against third-stage larvae of the parasitic nematode Angiostrongylus cantonensis, categorized according to the degree of motility reduction. Of the 108 crude samples and fractionated products, 48 showed some level of activity, with 13 reducing motility to 0-25% of the maximum exhibited, including two pure compounds, emethacin B and epicoccin E, neither previously known to exhibit anthelmintic properties. The process of bioassay-guided fractionation is illustrated in detail based on analysis of one of the crude extracts, which led to isolation of lamellicolic anhydride, a compound with moderate activity. This study validates the wMicroTracker system as an economical and high-throughput option for testing large suites of natural products against A. cantonensis, adds to the short list of diverse parasites for which it has been validated and highlights the value of A. cantonensis and Hawaiian fungi for discovery of new anthelmintics.
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