Identification of a nuclear receptor/coactivator developmental signaling pathway in the nematode parasite <i>Strongyloides stercoralis</i>
Mi Cheong Cheong, Zhu Wang, Tegegn G. Jaleta, Xinshe Li, James B. Lok, Steven A. Kliewer, David J. Mangelsdorf
Abstract
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.