{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T19:47:38Z","timestamp":1789069658914,"version":"build-2803163510"},"reference-count":18,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SCHA 1582\/7"],"award-info":[{"award-number":["SCHA 1582\/7"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2025,4,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              The protozoan\n              <jats:italic>Entamoeba gingivalis<\/jats:italic>\n              commonly colonizes anaerobic periodontal pockets, induces a severe innate immune response, invades gingival mucosa, and kills epithelial cells.\n              <jats:italic>E. gingivalis<\/jats:italic>\n              infection is associated with the common oral inflammatory disease periodontitis. DNA variants in vesicle-associated membrane proteins (VAMP) -3 and -8 genes are linked to increased periodontitis risk. These genes mediate host\u2013pathogen interactions, including mucin exocytosis to form protective barriers and matrix metalloproteinase (MMP) secretion in intestinal amoebiasis caused by\n              <jats:italic>Entamoeba histolytica<\/jats:italic>\n              . This study aimed to investigate the roles of VAMP3\/8 in gingival defense and\n              <jats:italic>E. gingivalis<\/jats:italic>\n              infection mechanisms. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 gene editing was used to create VAMP3\/8-deficient gingival epithelial cells and fibroblasts. Functional analyses included immunofluorescence, enzyme-linked immunosorbent assay (ELISA), cytotoxicity, and collagenase assays. VAMP8 co-localized with mucins in gingival epithelial cells (gECs), and VAMP3 with MMPs in gingival fibroblasts. In gECs\n              <jats:italic>, E. gingivalis<\/jats:italic>\n              infection increased mucin (MUC1: 3.6\u00d7, MUC21: 14.4\u00d7) and interleukin secretion (IL-8, IL-1B: &gt;6\u00d7,\n              <jats:italic>P<\/jats:italic>\n              = 0.019).\n              <jats:italic>VAMP8<\/jats:italic>\n              deficiency in gECs caused higher cell death (35% vs 4% in controls) with reduced exocytosis of mucins and interleukins. Likewise,\n              <jats:italic>E. gingivalis<\/jats:italic>\n              -induced VAMP8 translocation into lipid rafts was lost in VAMP8 knockout cells, validating the participation of VAMP8 in exocytosis. In wild-type but not VAMP3-deficient gingival fibroblasts,\n              <jats:italic>E. gingivalis<\/jats:italic>\n              strongly activated collagenases.\n              <jats:italic>E. gingivalis<\/jats:italic>\n              effects were more pathogenic than those of the oral anaerobic bacterium\n              <jats:italic>Porphyromonas gingivalis. E. gingivalis<\/jats:italic>\n              exploits VAMP8\/3-driven exocytosis pathways, driving inflammation and tissue destruction, underscoring its role as a significant periodontal pathogen.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/iai.00005-25","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T13:31:31Z","timestamp":1742563891000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["<i>Entamoeba gingivalis<\/i>\n            induces gingival cell death, collagen breakdown, and host immune response via VAMP8\/-3-driven exocytosis pathways"],"prefix":"10.1128","volume":"93","author":[{"given":"Lea","family":"Rosenfeld","sequence":"first","affiliation":[{"name":"Department of Periodontology, Oral Surgery and Oral Medicine, Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico","family":"Neumann","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Oral Surgery and Oral Medicine, Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Oral Surgery and Oral Medicine, Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayseg\u00fcl","family":"Adam","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Oral Surgery and Oral Medicine, Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5816-6765","authenticated-orcid":true,"given":"Arne S.","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Oral Surgery and Oral Medicine, Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.21-0120"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034512457373"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2015.140520"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034513490168"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034520901738"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1051\/parasite\/2014029"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1177\/00220345211004498"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1201394"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt299"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-31980-8"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01323-17"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12669"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2012.01752.x"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6142"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000070112.80711.3D"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.052761"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.17.1.463"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11811-8"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/iai.00005-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/iai.00005-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T13:09:05Z","timestamp":1744117745000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/iai.00005-25"}},"subtitle":[],"editor":[{"given":"Jeroen P. J.","family":"Saeij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,4,8]]},"references-count":18,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4,8]]}},"alternative-id":["10.1128\/iai.00005-25"],"URL":"https:\/\/doi.org\/10.1128\/iai.00005-25","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,8]]},"assertion":[{"value":"2025-01-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00005-25"}}