Proceedings of the National Academy of Sciences · 2021 · 24 citations · 27 references
Life SciencesDevelopmental BiologyMolecular BiologyDevelopmental SignalingGene ExpressionSignal TransductionHost-nematode InteractionsHost-parasite InteractionsNematode PathogenesisParasitic Disease PathogenesisParasitic PathogenesisCrispr-cas9 KnockoutDirected MutagenesisHost - Parasite Molecular InteractionsHost-parasite Molecular InteractionsLigand-dependent Gene ActivationMolecular Mechanisms Of InfectionNematode Infection MechanismsParasite Development
Significance Understanding the molecular mechanisms controlling nematode parasite infection is important to developing new therapeutic strategies. The DAF-12 nuclear receptor signaling pathway in free-living nematodes regulates a process known as the dauer diapause. In nematode parasites, this signaling pathway is believed to govern the infectious stage. To investigate this hypothesis, we characterized the orthologous components of DAF-12 and a parasite-specific transcriptional coactivator in the potentially lethal parasite Strongyloides stercoralis . Using a CRISPR method developed specifically for S. stercoralis , we demonstrate that DAF-12 and its coactivator are required for both the entry into and exit from the infectious stage. These studies further highlight the potential of therapeutically targeting this pathway in S. stercoralis and other nematode parasites.
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