Harnessing traditional medicine: A dual-action antimicrobial combination against pathogens.

The persistent threat of bacterial infections and escalating antibiotic resistance necessitates antimicrobial solutions. MAC4, a Malic Acid Combination inspired by Traditional Chinese Medicine, exhibits potent dual antibacterial and immunomodulatory effects. MAC4 demonstrates significant antibacterial activity, with minimum inhibitory concentrations (MIC) of 0.1C for E. coli and S. aureus, and 0.2C for P. aeruginosa and S. marcescens. It effectively disrupts bacterial biofilm formation, reducing biofilm mass and decreasing metabolic activity by over 94.97% at 2MIC and 4MIC concentrations. Transcriptomic analysis reveals MAC4 reprograms bacterial gene expression, with 1,150 differentially expressed genes affecting membrane, energy metabolism, and DNA replication. In an E. coli lung infection mouse model, MAC4 reduces bacterial load and modulates inflammation, downregulating IL-6, IL-1β, TNF-α, and preserving lung architecture. MAC4's dual-action capability, targeting both pathogen and host inflammation, positions it as a promising candidate for bacterial infections and inflammatory lung diseases, especially when conventional antibiotics are insufficient.