{"doi":"10.7554/elife.73535","title":"Characterization of the endogenous DAF-12 ligand and its use as an anthelmintic agent in Strongyloides stercoralis","abstract":"A prevalent feature of Strongyloides stercoralis is a life-long and potentially lethal infection that is due to the nematode parasite’s ability to autoinfect and, thereby, self-replicate within its host. Here, we investigated the role of the parasite’s nuclear receptor, Ss- DAF-12, in governing infection. We identified Δ7-DA as the endogenous Ss- DAF-12 ligand and elucidated the hormone’s biosynthetic pathway. Genetic loss of function of the ligand’s rate-limiting enzyme demonstrated that Δ7-DA synthesis is necessary for parasite reproduction, whereas its absence is required for the development of infectious larvae. Availability of the ligand permits Ss- DAF-12 to function as an on/off switch governing autoinfection, making it vulnerable to therapeutic intervention. In a preclinical model of hyperinfection, pharmacologic activation of DAF-12 suppressed autoinfection and markedly reduced lethality. Moreover, when Δ7-DA was administered with ivermectin, the current but limited drug of choice for treating strongyloidiasis, the combinatorial effects of the two drugs resulted in a near cure of the disease.","journal":"eLife","year":2021,"id":179067,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9462,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":513186,"name":"Mi Cheong Cheong","orcid":"0000-0002-7604-6203","position":1,"is_corresponding":false},{"id":725762,"name":"Jet Tsien","orcid":"0000-0002-2052-8051","position":2,"is_corresponding":false},{"id":726477,"name":"Heping Deng","orcid":null,"position":3,"is_corresponding":false},{"id":257961,"name":"Tian Qin","orcid":"0000-0001-7225-3224","position":4,"is_corresponding":false},{"id":439734,"name":"Jonathan D. C. Stoltzfus","orcid":"0000-0002-4006-5306","position":5,"is_corresponding":false},{"id":725763,"name":"Tegegn G. Jaleta","orcid":"0000-0002-0520-8033","position":6,"is_corresponding":false},{"id":726478,"name":"Xinshe Li","orcid":null,"position":7,"is_corresponding":false},{"id":473115,"name":"James B. Lok","orcid":"0000-0002-7611-8211","position":8,"is_corresponding":false},{"id":351406,"name":"Steven A. Kliewer","orcid":"0000-0001-5161-641X","position":9,"is_corresponding":false},{"id":351407,"name":"David J. Mangelsdorf","orcid":"0000-0002-4355-0796","position":10,"is_corresponding":false},{"id":439733,"name":"Zhu Wang","orcid":"0000-0003-0768-0988","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-18T23:47:44.875897Z","pmid":"34874004","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}