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 <i>E. coli</i> and <i>S. aureus</i>, and 0.2C for <i>P. aeruginosa</i> and <i>S. marcescens</i>. 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 <i>E. coli</i> lung infection mouse model, MAC4 reduces bacterial load and modulates inflammation, downregulating <i>IL-6</i>, <i>IL-1β</i>, <i>TNF-α</i>, 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.