{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T17:46:11Z","timestamp":1770831971166,"version":"3.50.1"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Seventh Framework Programme for Research and Technological Development","award":["279185"],"award-info":[{"award-number":["279185"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["668303"],"award-info":[{"award-number":["668303"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL-125128"],"award-info":[{"award-number":["HL-125128"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013342","name":"NIHR Imperial Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013342","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009187","name":"Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009187","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000762","name":"Imperial College Healthcare NHS Trust","doi-asserted-by":"publisher","award":["70931"],"award-info":[{"award-number":["70931"]}],"id":[{"id":"10.13039\/501100000762","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Neisseria meningitidis (Nm) is a nasopharyngeal commensal carried by healthy individuals. However, invasive infections occurs in a minority of individuals, with devastating consequences. There is evidence that common polymorphisms are associated with invasive meningococcal disease (IMD), but the contributions of rare variants other than those in the complement system have not been determined.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We identified familial cases of IMD in the UK meningococcal disease study and the European Union Life-Threatening Infectious Disease Study. Candidate genetic variants were identified by whole-exome sequencing of 2 patients with familial IMD. Candidate variants were further validated by in vitro assays.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Exomes of 2 siblings with IMD identified a novel heterozygous missense mutation in BPIFA1\/SPLUNC1. Sequencing of 186 other nonfamilial cases identified another unrelated IMD patient with the same mutation. SPLUNC1 is an innate immune defense protein expressed in the nasopharyngeal epithelia; however, its role in invasive infections is unknown. In vitro assays demonstrated that recombinant SPLUNC1 protein inhibits biofilm formation by Nm, and impedes Nm adhesion and invasion of human airway cells. The dominant negative mutant recombinant SPLUNC1 (p.G22E) showed reduced antibiofilm activity, increased meningococcal adhesion, and increased invasion of cells, compared with wild-type SPLUNC1.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>A mutation in SPLUNC1 affecting mucosal attachment, biofilm formation, and invasion of mucosal epithelial cells is a new genetic cause of meningococcal disease.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciz600","type":"journal-article","created":{"date-parts":[[2019,6,29]],"date-time":"2019-06-29T11:08:03Z","timestamp":1561806483000},"page":"2045-2053","source":"Crossref","is-referenced-by-count":7,"title":["A Rare Mutation in <i>SPLUNC1<\/i> Affects Bacterial Adherence and Invasion in Meningococcal Disease"],"prefix":"10.1093","volume":"70","author":[{"given":"Bayarchimeg","family":"Mashbat","sequence":"first","affiliation":[{"name":"Department of Paediatric Infectious Diseases, Division of Medicine, Imperial College London, Norfolk Place, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evangelos","family":"Bellos","sequence":"additional","affiliation":[{"name":"Department of Paediatric Infectious Diseases, Division of Medicine, Imperial College London, Norfolk Place, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Hodeib","sequence":"additional","affiliation":[{"name":"Department of Paediatric Infectious Diseases, Division of Medicine, Imperial College London, Norfolk Place, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fadil","family":"Bidmos","sequence":"additional","affiliation":[{"name":"Department of Paediatric Infectious Diseases, Division of Medicine, Imperial College London, Norfolk Place, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan S","family":"Thwaites","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaxuan","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Paediatric Infectious Diseases, Division of Medicine, Imperial College London, Norfolk Place, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria J","family":"Wright","sequence":"additional","affiliation":[{"name":"Department of Paediatric Infectious Diseases, Division of Medicine, Imperial College London, Norfolk Place, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jethro A","family":"Herberg","sequence":"additional","affiliation":[{"name":"Department of Paediatric Infectious Diseases, Division of Medicine, Imperial College London, Norfolk Place, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela S","family":"Klobassa","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adolescence Surgery, Division of General Pediatric Surgery, Medical University Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William G","family":"Walton","sequence":"additional","affiliation":[{"name":"Paediatric Intensive Care Unit, St. Mary\u2019s Hospital, Imperial College Healthcare Trust, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Werner","family":"Zenz","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adolescence Surgery, Division of General Pediatric Surgery, Medical University Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trevor T","family":"Hansel","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Nadel","sequence":"additional","affiliation":[{"name":"Paediatric Intensive Care Unit, St. Mary\u2019s Hospital, Imperial College Healthcare Trust, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul R","family":"Langford","sequence":"additional","affiliation":[{"name":"Department of Paediatric Infectious Diseases, Division of Medicine, Imperial College London, Norfolk Place, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luregn J","family":"Schlapbach","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Brisbane, The University of Queensland Brisbane, Australia"},{"name":"Paediatric Critical Care Research Group, The University of Queensland Brisbane, Australia"},{"name":"Paediatric Intensive Care Unit, Lady Cilento Children\u2019s Hospital, Children\u2019s Health Queensland, Brisbane, Australia"},{"name":"Department of Pediatrics, Bern University Hospital, Inselspital, University of Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Shi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Paediatric Infectious Diseases, Division of Medicine, Imperial College London, Norfolk Place, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew R","family":"Redinbo","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of North Carolina, Chapel Hill"},{"name":"Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill"},{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y Peter","family":"Di","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, University of Pittsburgh, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Levin","sequence":"additional","affiliation":[{"name":"Department of Paediatric Infectious Diseases, Division of Medicine, Imperial College London, Norfolk Place, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa","family":"Sancho-Shimizu","sequence":"additional","affiliation":[{"name":"Department of Paediatric Infectious Diseases, Division of Medicine, Imperial College London, Norfolk Place, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,7,1]]},"reference":[{"key":"2022052415063073400_CIT0001","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1099\/jmm.0.45529-0","article-title":"Neisseria meningitidis: an overview of the carriage state","volume":"53","author":"Yazdankhah","year":"2004","journal-title":"J Med 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