{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T07:05:24Z","timestamp":1774940724019,"version":"3.50.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Fusobacterium nucleatum<\/jats:italic>\n                      is a Gram-negative obligate anaerobic bacterium with trans-organ pathogenicity. It serves as a crucial pathogen causing intracranial anaerobic infections and is closely associated with the occurrence of brain abscess. However, the mechanism by which\n                      <jats:italic>Fusobacterium nucleatum<\/jats:italic>\n                      crosses the blood-brain barrier and induces intracranial infection remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study,\n                      <jats:italic>Fusobacterium nucleatum<\/jats:italic>\n                      clinical strain isolated from the brain abscess was identified and characterized. Its growth characteristics and biofilm-forming capacity were compared with those of the ATCC 25586 standard strain. Furthermore, the adhesive and invasive capabilities of both strains towards oral epithelial cells and brain microvascular endothelial cells were assessed. An\n                      <jats:italic>in vitro<\/jats:italic>\n                      BBB model was constructed using a brain microvascular endothelial monolayer to examine the effects of bacterial infection on the expression of tight junction proteins (occludin, Claudin-5, ZO-1). Finally, antimicrobial susceptibility testing combined with proteomic techniques was employed to analyze the antibiotic resistance profiles and differentially expressed proteins of the strains.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>One clinical strain was successfully isolated and identified from specimens of 7 brain abscess patients. Compared to the standard strain, the clinical isolate demonstrated a slower growth rate, reduced biofilm formation, and diminished adhesion and invasion capabilities against both oral epithelial cells and brain microvascular endothelial cells. The two strains exhibited significantly distinct regulatory patterns on the tight junction protein expression in brain microvascular endothelial cells. Proteomic analysis revealed extensive protein reprogramming in the clinical strain, characterized by the upregulation of proteins involved in metabolic pathways and immune evasion. Altered antimicrobial susceptibility in the clinical strain correlated with differential expression of proteins such as ribosomal components and efflux pump proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Fusobacterium nucleatum<\/jats:italic>\n                      can specifically adhere to and invade brain microvascular endothelial cells, disrupting their tight junctions. Through proteomic reprogramming,\n                      <jats:italic>Fusobacterium nucleatum<\/jats:italic>\n                      enhances its metabolic adaptation and immune evasion capabilities to adapt to changes in the intracranial microenvironment and establish persistent infection, thereby achieving a strategic shift from barrier penetration to intracranial colonization.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1719385","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:33:40Z","timestamp":1774935220000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Reprogramming of pathogenic strategies in Fusobacterium nucleatum: a study based on an in vitro infection model"],"prefix":"10.3389","volume":"16","author":[{"given":"Li","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Preventive and Pediatric Dentistry, School and Hospital of Stomatology, Tianjin Medical University","place":["Tianjin, China"]},{"name":"Department of Preventive and Pediatric Dentistry, Tianjin Medical University School and Hospital of Stomatology & Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Preventive and Pediatric Dentistry, School and Hospital of Stomatology, Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenyu","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, Anyang Hospital of Stomatology","place":["Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Preventive and Pediatric Dentistry, School and Hospital of Stomatology, Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianquan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Baodi Hospital, Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Preventive and Pediatric Dentistry, School and Hospital of Stomatology, Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Pu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Tianjin Huanhu Hospital","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.nbd.2009.07.030","article-title":"Structure and function of the blood-brain barrier","volume":"37","author":"Abbott","year":"2010","journal-title":"Neurobiol. 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