Endothelial barrier disruption and contact system modulation during bacterial infection

This review examines how bacterial pathogens disrupt vascular barrier integrity and manipulate coagulation with a focus on endothelial signaling pathways, bacterial effectors, and contextual determinants of host-pathogen interactions. Particular attention is given to a contact activation system member, factor XII (FXII), that operates in infection not merely via coagulation but also through immune modulation and direct antimicrobial activity.

Emerging work reveals that loss of endothelial barrier integrity arises from both inflammatory cues and pathogen-directed manipulation of junctional complexes, the glycocalyx, and cell death programs such as pyroptosis. These mechanisms are influenced by pathogen diversity, tissue-specific environments, and heterogeneity across experimental models. Studies demonstrate that FXII function is context-dependent, supporting pathogen containment through fibrin deposition in some infections, yet promoting inflammation and dissemination in others. Additionally, pathogens such as Acinetobacter baumannii directly inhibit FXII, thereby impairing immune defense and coagulation-driven containment.

Therapeutic efforts now increasingly target endothelial stabilization and coagulation-immune crosstalk, yet outcomes depend on timing, infectious context, and host state. While approaches such as glycocalyx restoration, inflammasome inhibition, and FXII-based biomimetics show promise, successful intervention will likely require combination strategies that preserve host defense while limiting vascular damage. Given the diversity of host-pathogen interactions, no single therapy is expected to be universally effective.