Vimentin–NF-κB signaling contributing to IbeA-mediated adhesion, invasion, and biofilm formation during Escherichia coli K1 traversal of the blood–brain barrier

Introduction: K1 meningitis. However, it is unclear how IbeA coordinates its role in bacterial adhesion, invasion, and biofilm formation during crossing the blood-brain barrier (BBB). Methods: experiments. Results: and VIM significantly impaired bacterial adhesion, invasion, and biofilm formation both on HBMECs and on abiotic surfaces. In neonatal rats, infection with ZD1 resulted in higher survival rates, milder neurological symptoms, and a marked reduction of biofilm structures within the cerebral microvasculature compared with infection by the wild-type strain. IbeA-triggered post-translational modifications and cytoplasmic mobilization of VIM drive its nuclear translocation, which in turn activates NF-κB signaling. Pharmacological inhibition of VIM with GA disrupted IbeA-mediated virulence, lowering bacterial loads in the blood and alleviating neurological injury. Conclusions: K1 adhesion, invasion, and biofilm formation by activating the VIM-NF-κB signaling pathway. Our study establishes for the first time a direct mechanistic link between IbeA's multiple virulence functions through the above signaling pathway leading to acute BBB disruption and meningitis and identify GA as a potential drug development candidate for this disease.