{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T11:50:25Z","timestamp":1791633025924,"version":"4.3.4"},"reference-count":46,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["APMIS"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Enterococcus faecalis<\/jats:italic>\n                    <\/jats:styled-content>\n                    is a commensal of the human gastrointestinal microbiota that has emerged as a successful opportunistic pathogen associated with persistent infections, antimicrobial resistance, and biofilm formation. Increasing evidence indicates that iron availability functions as a master environmental signal coordinating\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>E. faecalis<\/jats:italic>\n                    <\/jats:styled-content>\n                    pathogenic traits. This review summarizes clinical, molecular, and sequencing\u2010based studies linking iron homeostasis to extracellular DNA (eDNA) dynamics, biofilm architecture, virulence regulation, and immune evasion, and critically evaluates the emerging but still associative evidence connecting\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>E. faecalis<\/jats:italic>\n                    <\/jats:styled-content>\n                    to colorectal carcinogenesis. We highlight how iron sensing and uptake systems modulate biofilm stability through eDNA release, metabolic cooperation, and transcriptional control via the ferric uptake regulator (Fur) and other regulatory networks. We further integrate experimental findings that suggest how these mechanisms may promote inflammation\u2010driven tumorigenesis in the colon, although a complete causal pathway has not yet been established. Finally, we discuss translational implications, including iron\u2010targeting and eDNA\u2010disruptive strategies as promising anti\u2010virulence approaches, and identify key knowledge gaps requiring future investigation. This review positions iron metabolism at the center of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>E. faecalis<\/jats:italic>\n                    <\/jats:styled-content>\n                    pathogenicity and underscores its potential as a therapeutic target, while recognizing the need for further mechanistic and clinical validation.\n                  <\/jats:p>","DOI":"10.1111\/apm.70268","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:07:25Z","timestamp":1790957245000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Iron, Biofilm, and Colorectal Cancer: Mechanistic Insights Into\n                    <scp>\n                      <i>Enterococcus faecalis<\/i>\n                    <\/scp>\n                    Pathogenesis"],"prefix":"10.1111","volume":"134","author":[{"given":"Sibusiso","family":"Luthuli","sequence":"first","affiliation":[{"name":"Department of Precision Medicine University of Campania \u2018L. Vanvitelli\u2019  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2590-370X","authenticated-orcid":false,"given":"Nathalie","family":"Scarpulla","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine University of Campania \u2018L. Vanvitelli\u2019  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Bertolino","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine University of Campania \u2018L. Vanvitelli\u2019  Naples Italy"},{"name":"Unit of Internal Medicine and Transplants Monaldi Hospital  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulama","family":"Luthuli","sequence":"additional","affiliation":[{"name":"Department of Paediatric Surgery University of Pretoria, Kalafong and Steve Biko Academic Hospital of the University of Pretoria  Pretoria South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5381-3537","authenticated-orcid":false,"given":"Emanuele","family":"Durante\u2010Mangoni","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine University of Campania \u2018L. Vanvitelli\u2019  Naples Italy"},{"name":"Unit of Internal Medicine and Transplants Monaldi Hospital  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"e_1_2_20_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2761"},{"key":"e_1_2_20_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-025-11399-z"},{"key":"e_1_2_20_4_1","doi-asserted-by":"publisher","DOI":"10.3109\/1040841X.2013.841639"},{"key":"e_1_2_20_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2836"},{"issue":"6","key":"e_1_2_20_6_1","article-title":"Metabolic Interplay Between Gut Microbiota and the Host: Iron Acquisition in \n                     Enterococcus faecalis","volume":"14","author":"Lam L. N.","year":"2018","journal-title":"PLoS Pathogens"},{"issue":"3","key":"e_1_2_20_7_1","article-title":"Iron Availability Modulates Extracellular DNA Release and Biofilm Formation in Nutrient\u2010Starved \n                     Enterococcus faecalis","volume":"207","author":"Zhen X.","year":"2025","journal-title":"Journal of Bacteriology"},{"key":"e_1_2_20_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1433313"},{"key":"e_1_2_20_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens12010034"},{"key":"e_1_2_20_10_1","doi-asserted-by":"publisher","DOI":"10.3947\/ic.2017.49.1.51"},{"key":"e_1_2_20_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00626-17"},{"key":"e_1_2_20_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00496-22"},{"key":"e_1_2_20_13_1","doi-asserted-by":"crossref","unstructured":"D. N.Brunson H.Manzer A. B.Smith J. P.Zackular T.Kitten andJ. A.Lemos \u201cA Novel Heme\u2010Degrading Enzyme That Regulates Heme and Iron Homeostasis and Promotes Virulence inEnterococcus faecalis \u201dbioRxiv(2025): 2025.01.20.633879.","DOI":"10.1101\/2025.01.20.633879"},{"key":"e_1_2_20_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.00615-21"},{"key":"e_1_2_20_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00203-022-03309-7"},{"key":"e_1_2_20_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.01580"},{"key":"e_1_2_20_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023948"},{"key":"e_1_2_20_18_1","volume-title":"Identificaci\u00f3n de ARN no Codificantes Relacionados a Sistemas de Homeostasis de Hierro en Enterococcus faecalis","author":"G\u00f3mez Contreras S. 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