{"doi":"10.1101/2023.08.10.552843","title":"Transcriptional suppression of sphingolipid catabolism controls pathogen resistance in <i>C. elegans</i>","abstract":"ABSTRACT Sphingolipids are required for diverse biological functions and are degraded by specific catabolic enzymes. However, the mechanisms that regulate sphingolipid catabolism are not known. Here we characterize a transcriptional axis that regulates sphingolipid breakdown to control resistance against bacterial infection. From an RNAi screen for transcriptional regulators of pathogen resistance in the nematode C. elegans , we identified the nuclear hormone receptor nhr-66, a ligand-gated transcription factor homologous to human hepatocyte nuclear factor 4. Tandem chromatin immunoprecipitation-sequencing and RNA sequencing experiments revealed that NHR-66 is a transcriptional repressor, which directly targets sphingolipid catabolism genes. Transcriptional de-repression of two sphingolipid catabolic enzymes in nhr-66 loss-of-function mutants drives the breakdown of sphingolipids, which enhances host susceptibility to infection with the bacterial pathogen Pseudomonas aeruginosa . These data define transcriptional control of sphingolipid catabolism in the regulation of cellular sphingolipids, a process that is necessary for pathogen resistance.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":400417,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":306038,"name":"Nicholas Peterson","orcid":"0000-0003-4157-8119","position":1,"is_corresponding":false},{"id":821961,"name":"J. Elizabeth Salisbury","orcid":null,"position":2,"is_corresponding":false},{"id":306037,"name":"Pengpeng Liu","orcid":"0000-0002-4891-8780","position":3,"is_corresponding":false},{"id":1091863,"name":"Amanda L. Page","orcid":null,"position":4,"is_corresponding":false},{"id":1005019,"name":"Samantha Y. Tse","orcid":"0000-0002-9493-4538","position":5,"is_corresponding":false},{"id":571215,"name":"Khursheed A. Wani","orcid":"0000-0003-3559-7962","position":6,"is_corresponding":false},{"id":639027,"name":"Claire E. Tocheny","orcid":"0000-0002-5791-7560","position":7,"is_corresponding":false},{"id":306040,"name":"Read Pukkila-Worley","orcid":"0000-0001-5340-8294","position":8,"is_corresponding":false},{"id":1091276,"name":"Mohamad Nasrallah","orcid":"0000-0001-6434-5305","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T01:20:04.010538Z","pmid":null,"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":[]}