{"doi":"10.1128/mbio.04015-24","title":"SARS-CoV-2 infectivity can be modulated through bacterial grooming of the glycocalyx","abstract":"ABSTRACT The gastrointestinal (GI) tract is a site of replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and GI symptoms are often reported by patients. SARS-CoV-2 cell entry depends upon heparan sulfate (HS) proteoglycans, which commensal bacteria that bathe the human mucosa are known to modify. To explore human gut HS-modifying bacterial abundances and how their presence may impact SARS-CoV-2 infection, we developed a task-based analysis of proteoglycan degradation on large-scale shotgun metagenomic data. We observed that gut bacteria with high predicted catabolic capacity for HS differ by age and sex, factors associated with coronavirus disease 2019 (COVID-19) severity, and directly by disease severity during/after infection, but do not vary between subjects with COVID-19 comorbidities or by diet. Gut commensal bacterial HS-modifying enzymes reduce spike protein binding and infection of authentic SARS-CoV-2, suggesting that bacterial grooming of the GI mucosa may impact viral susceptibility. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019, can infect the gastrointestinal (GI) tract, and individuals who exhibit GI symptoms often have more severe disease. The GI tract’s glycocalyx, a component of the mucosa covering the large intestine, plays a key role in viral entry by binding SARS-CoV-2’s spike protein via heparan sulfate (HS). Here, using metabolic task analysis of multiple large microbiome sequencing data sets of the human gut microbiome, we identify a key commensal human intestinal bacteria capable of grooming glycocalyx HS and modulating SARS-CoV-2 infectivity in vitro . Moreover, we engineered the common probiotic Escherichia coli Nissle 1917 (EcN) to effectively block SARS-CoV-2 binding and infection of human cell cultures. Understanding these microbial interactions could lead to better risk assessments and novel therapies targeting viral entry mechanisms.","journal":"mBio","year":2025,"id":525297,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9631,"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":106554,"name":"Benjamin P. Kellman","orcid":"0000-0002-0780-6096","position":1,"is_corresponding":false},{"id":106533,"name":"Daniel R. Sandoval","orcid":"0000-0002-7938-315X","position":2,"is_corresponding":false},{"id":106532,"name":"Thomas Mandel Clausen","orcid":"0000-0001-7543-9622","position":3,"is_corresponding":false},{"id":292740,"name":"Robert Cooper","orcid":"0000-0003-2136-0403","position":4,"is_corresponding":false},{"id":1400058,"name":"Alhosna Benjdia","orcid":"0000-0002-3544-2541","position":5,"is_corresponding":false},{"id":833119,"name":"Feryel Soualmia","orcid":"0000-0003-1818-703X","position":6,"is_corresponding":false},{"id":249772,"name":"Alex E. Clark","orcid":"0000-0003-1687-416X","position":7,"is_corresponding":false},{"id":106549,"name":"Aaron F. Garretson","orcid":"0000-0003-3855-4482","position":8,"is_corresponding":false},{"id":499161,"name":"Clarisse Marotz","orcid":"0000-0002-1520-8854","position":9,"is_corresponding":false},{"id":552309,"name":"Se Jin Song","orcid":"0000-0003-0750-5709","position":10,"is_corresponding":false},{"id":347187,"name":"Stephen Wandro","orcid":"0000-0001-5514-0244","position":11,"is_corresponding":false},{"id":268001,"name":"Lívia S. Zaramela","orcid":"0000-0002-1065-3799","position":12,"is_corresponding":false},{"id":270109,"name":"Rodolfo A. Salido","orcid":"0000-0003-0631-2817","position":13,"is_corresponding":false},{"id":107902,"name":"Qiyun Zhu","orcid":"0000-0002-3568-6271","position":14,"is_corresponding":false},{"id":106295,"name":"Erick Armingol","orcid":"0000-0002-1546-9165","position":15,"is_corresponding":false},{"id":3557,"name":"Yoshiki Vázquez‐Baeza","orcid":"0000-0001-6014-2009","position":16,"is_corresponding":false},{"id":3535,"name":"Daniel McDonald","orcid":"0000-0003-0876-9060","position":17,"is_corresponding":false},{"id":374072,"name":"James T. Sorrentino","orcid":"0000-0002-7058-9987","position":18,"is_corresponding":false},{"id":106948,"name":"Bryn C. Taylor","orcid":"0000-0002-4957-5417","position":19,"is_corresponding":false},{"id":225242,"name":"Pedro Belda‐Ferre","orcid":"0000-0001-6532-1161","position":20,"is_corresponding":false},{"id":653690,"name":"Promi Das","orcid":"0000-0001-6733-2059","position":21,"is_corresponding":false},{"id":555806,"name":"Farhana Ali","orcid":"0000-0003-3741-4410","position":22,"is_corresponding":false},{"id":375307,"name":"Chenguang Liang","orcid":null,"position":23,"is_corresponding":false},{"id":3631,"name":"Yujie Zhang","orcid":"0000-0002-1017-0316","position":24,"is_corresponding":false},{"id":397732,"name":"Luca Schifanella","orcid":"0000-0002-6123-536X","position":25,"is_corresponding":false},{"id":1400059,"name":"Alice Covizzi","orcid":"0000-0001-5368-2883","position":26,"is_corresponding":false},{"id":1056425,"name":"Alessia Lai","orcid":"0000-0002-3174-5721","position":27,"is_corresponding":false},{"id":218069,"name":"Agostino Riva","orcid":"0000-0003-3171-3049","position":28,"is_corresponding":false},{"id":1281717,"name":"Christopher M. Basting","orcid":"0009-0001-7744-3673","position":29,"is_corresponding":false},{"id":735621,"name":"Courtney A. Broedlow","orcid":null,"position":30,"is_corresponding":false},{"id":5023,"name":"Aki S. Havulinna","orcid":"0000-0002-4787-8959","position":31,"is_corresponding":false},{"id":270113,"name":"Pekka Jousilahti","orcid":"0000-0001-7190-0979","position":32,"is_corresponding":false},{"id":654775,"name":"Mehrbod Estaki","orcid":"0000-0003-4556-8444","position":33,"is_corresponding":false},{"id":3556,"name":"Tomasz Kościółek","orcid":"0000-0002-9915-7387","position":34,"is_corresponding":false},{"id":297642,"name":"Rayus Kuplicki","orcid":"0000-0003-2954-6421","position":35,"is_corresponding":false},{"id":510373,"name":"Teresa A. Victor","orcid":"0000-0002-0112-2902","position":36,"is_corresponding":false},{"id":242790,"name":"Martin P. Paulus","orcid":"0000-0002-0825-3606","position":37,"is_corresponding":false},{"id":386844,"name":"Kristen E. Savage","orcid":null,"position":38,"is_corresponding":false},{"id":386845,"name":"Jennifer L. Benbow","orcid":null,"position":39,"is_corresponding":false},{"id":386152,"name":"Emma S. Spielfogel","orcid":"0000-0002-9006-239X","position":40,"is_corresponding":false},{"id":247230,"name":"Cheryl A.M. Anderson","orcid":"0000-0002-1877-6873","position":41,"is_corresponding":false},{"id":306375,"name":"Maria Elena Martinez","orcid":null,"position":42,"is_corresponding":false},{"id":104605,"name":"James V. Lacey","orcid":"0000-0002-4560-8592","position":43,"is_corresponding":false},{"id":16592,"name":"Shi Huang","orcid":"0000-0002-7529-2269","position":44,"is_corresponding":false},{"id":255417,"name":"Niina Haiminen","orcid":"0000-0002-8663-1019","position":45,"is_corresponding":false},{"id":3223,"name":"Laxmi Parida","orcid":"0000-0002-7872-5074","position":46,"is_corresponding":false},{"id":255424,"name":"Ho‐Cheol Kim","orcid":"0000-0003-0464-4340","position":47,"is_corresponding":false},{"id":19768,"name":"Jack A. Gilbert","orcid":"0000-0001-7920-7001","position":48,"is_corresponding":false},{"id":103441,"name":"Daniel A Sweeney","orcid":null,"position":49,"is_corresponding":false},{"id":555816,"name":"Sarah M. Allard","orcid":"0000-0001-7626-0472","position":50,"is_corresponding":false},{"id":3540,"name":"Austin D. Swafford","orcid":"0000-0001-5655-8300","position":51,"is_corresponding":false},{"id":270108,"name":"Susan Cheng","orcid":"0000-0002-4977-036X","position":52,"is_corresponding":false},{"id":33743,"name":"Michael Inouye","orcid":"0000-0001-9413-6520","position":53,"is_corresponding":false},{"id":270115,"name":"Teemu Niiranen","orcid":"0000-0002-7394-7487","position":54,"is_corresponding":false},{"id":233460,"name":"Mohit Jain","orcid":"0000-0001-8628-2069","position":55,"is_corresponding":false},{"id":1112,"name":"Veikko Salomaa","orcid":"0000-0001-7563-5324","position":56,"is_corresponding":false},{"id":268003,"name":"Karsten Zengler","orcid":"0000-0002-8062-3296","position":57,"is_corresponding":false},{"id":332551,"name":"Nichole R. Klatt","orcid":"0000-0003-2968-5480","position":58,"is_corresponding":false},{"id":293818,"name":"Jeff Hasty","orcid":null,"position":59,"is_corresponding":false},{"id":1400060,"name":"Olivier Berteau","orcid":"0000-0002-3434-5168","position":60,"is_corresponding":false},{"id":103778,"name":"Aaron F. Carlin","orcid":"0000-0002-1669-8066","position":61,"is_corresponding":false},{"id":106562,"name":"Jeffrey D. Esko","orcid":"0000-0001-8322-1834","position":62,"is_corresponding":false},{"id":106296,"name":"Nathan E. Lewis","orcid":"0000-0001-7700-3654","position":63,"is_corresponding":false},{"id":3554,"name":"Rob Knight","orcid":"0000-0002-0975-9019","position":64,"is_corresponding":false},{"id":106555,"name":"Cameron Martino","orcid":"0000-0001-9334-1258","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:50:21.274116Z","pmid":"39998226","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":[]}