Monosodium Glutamate Inhibits Pseudomonas aeruginosa-Induced Acute Lung Injury by Targeting the Type III Secretion Systems and Modulating Host Immunity

The opportunistic pathogen <i>Pseudomonas aeruginosa</i> poses a serious threat to immunocompromised patients. Monosodium glutamate (MSG), a widely used flavor enhancer, has been reported to possess anti-inflammatory and antioxidant properties. However, its therapeutic potential and mechanism against <i>Pseudomonas aeruginosa</i> (<i>P. aeruginosa</i>) infection have remained unexplored. This study systematically elucidated the protective effects and molecular mechanisms of MSG against <i>P. aeruginosa</i>-induced acute lung injury (ALI). In a murine pneumonia model, MSG administration effectively alleviated lung pathological damage, edema, and inflammatory responses. Mechanistically, MSG exerted protection through a multifaceted strategy, including direct suppression of bacterial virulence via binding to PopB of T3SS inhibition of the TLR4/MyD88/MAPK-driven inflammatory cascade and pro-inflammatory cytokine production, enhancement of endogenous antioxidant defense (SOD, CAT), and reshaping of pulmonary macrophages from the M1 to M2 phenotype. Notably, the anti-virulence effect of MSG, achieved by binding to PopB (K_D = 3.52 × 10^-6 M), presented a distinct advantage over traditional antimicrobials by potentially mitigating resistance development. Collectively, these findings indicated that MSG can alleviate ALI caused by <i>P. aeruginosa</i> infection.