Reprogramming of pathogenic strategies in Fusobacterium nucleatum: a study based on an in vitro infection model

Background: crosses the blood-brain barrier and induces intracranial infection remains unclear. Methods: 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. Results: 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. Conclusion: 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.