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

## TL;DR

Monosodium glutamate (MSG) reduces lung damage from Pseudomonas aeruginosa infection by targeting bacterial virulence and boosting the body's defenses.

## Contribution

This study reveals that MSG inhibits Pseudomonas aeruginosa-induced lung injury by targeting T3SS and modulating host immunity.

## Key findings

- MSG alleviates lung damage, edema, and inflammation in a murine pneumonia model.
- MSG suppresses bacterial virulence by binding to PopB of T3SS and inhibiting inflammatory pathways.
- MSG enhances antioxidant defenses and shifts macrophages from M1 to M2 phenotype.

## Abstract

The opportunistic pathogen Pseudomonas aeruginosa 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 Pseudomonas aeruginosa (P. aeruginosa) infection have remained unexplored. This study systematically elucidated the protective effects and molecular mechanisms of MSG against P. aeruginosa-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 (KD = 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 P. aeruginosa infection.