Proteomic Remodeling of the Cochlea During Chronic Suppurative Otitis Media Reveals Immune-Driven Injury Pathways

Chronic suppurative otitis media (CSOM) is a persistent middle ear infection in which chronic inflammation drives irreversible sensorineural hearing loss (SNHL), yet the molecular mechanisms linking middle ear chronic infection to cochlear injury remain poorly defined. Using a murine model of CSOM induced by Pseudomonas aeruginosa (PA) persisters, a quantitative proteomic profiling of cochlear tissue was performed at seven days post-infection. Mass spectrometry revealed over 250 proteins that were significantly altered, indicating broad immune activation, oxidative stress, and disruption of ion homeostasis. Among the top candidates, HSPA5, MPO, and ATP2A2 were strongly associated with inflammatory stress and cellular injury pathways. These findings identify immunometabolic remodeling and macrophage-driven inflammation as central mechanisms linking chronic middle ear infection to cochlear injury.