his study reveals that EphA2 protects the blood-brain barrier (BBB) during Streptococcus suis infection by mediating autophagy. The pathogen subverts this defense by using its serine/threonine kinase (STK) to trigger a signaling cascade (SIRT1/DCAF15) that promotes EphA2 ubiquitination and degradation, thereby disrupting the BBB. These findings identify EphA2 as a potential therapeutic target for bacterial meningitis.