{"doi":"10.1016/j.celrep.2025.116304","title":"Mucus-derived glycans are inhibitory signals for Salmonella Typhimurium SPI-1-mediated invasion","abstract":"Mucus forms a critical barrier against enteric pathogens like Salmonella enterica serovar Typhimurium. While in vivo studies indicate that secreted, gel-forming mucins and specifically core 3 glycosylation are protective against S. Typhimurium, the molecular mechanisms involved remain unclear. Here, we demonstrate that native intestinal mucins inhibit Salmonella invasion of colonic epithelial cells by downregulating the type 3 secretion system through suppression of the key virulence regulator, HilD. Our study identifies mucin glycans and specific mucin sugars, namely N-acetyl galactosamine and N-acetyl glucosamine, as the components responsible for mucin's anti-virulence effect, likely via functional or direct interaction with HilD's putative carbohydrate-binding domain. Notably, we find that the native presentation of these sugars is important for activity. These insights provide a mechanistic foundation for mucin-based strategies to combat enteric infections and, given the prevalence of homologous AraC-type regulators in other pathogens, suggest mucins' potential as broad-spectrum anti-virulence agents.","journal":"Cell Reports","year":2025,"id":518714,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1386609,"name":"Michaela A. Gold","orcid":"0000-0002-0605-1971","position":1,"is_corresponding":false},{"id":1212192,"name":"Corey A. Stevens","orcid":"0000-0002-9619-7869","position":2,"is_corresponding":false},{"id":1386610,"name":"Karsten Tedin","orcid":"0000-0003-2109-0730","position":3,"is_corresponding":false},{"id":1386611,"name":"Amanda M. Wood","orcid":"0009-0009-8648-2437","position":4,"is_corresponding":false},{"id":1231944,"name":"Deniz Uzun","orcid":null,"position":5,"is_corresponding":false},{"id":1386612,"name":"Gerardo Cárcamo-Oyarce","orcid":"0009-0004-4827-4892","position":6,"is_corresponding":false},{"id":1094314,"name":"Bradley S. Turner","orcid":"0000-0001-8086-2118","position":7,"is_corresponding":false},{"id":782098,"name":"Marcus Fulde","orcid":null,"position":8,"is_corresponding":false},{"id":355479,"name":"Jeongmin Song","orcid":"0000-0002-6777-3505","position":9,"is_corresponding":false},{"id":872815,"name":"Jessica R. Kramer","orcid":"0000-0002-4268-0126","position":10,"is_corresponding":false},{"id":290720,"name":"Katharina Ribbeck","orcid":"0000-0001-8260-338X","position":11,"is_corresponding":false},{"id":290719,"name":"Kelsey M. Wheeler","orcid":"0000-0001-5947-5025","position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":null,"created_at":"2026-07-19T02:49:14.184995Z","pmid":"40992372","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":[]}