Abstract
Acinetobacter baumannii is a major nosocomial pathogen causing pneumonia; its virulence, biofilm formation, and antibiotic resistance are all regulated by quorum sensing (QS). Nerol, a monoterpene derived from orange peel, exhibits antibacterial activity. This study demonstrates that Nerol exhibits a minimum inhibitory concentration (MIC(90)) of 0.5 mg/mL against A. baumannii. At subinhibitory concentrations, it inhibits N-acyl-homoserine lactones, biofilm formation, motility, and extracellular polymeric substance (EPS) production. Proteomics revealed synchronous downregulation of virulence proteins, including BfmS, YiaD_1, MacB, MurF, and MtgA. ITC confirmed its 2:1 stoichiometric, exothermic binding to the BfmS sensor domain (KD 1.3 × 10(-4) M), disrupting the BfmRS two-component system and blocking downstream QS pathways. Experiments demonstrated that Nerol significantly reduced the gene expression and protein secretion levels of proinflammatory cytokines (TNF-α, IL-6, and IL-1β) by inhibiting the activation of the NF-κB/MAPK signaling cascade. Nerol's ability to counteract QS and alleviate inflammatory responses highlights its potential as a therapeutic agent for treating A. baumannii infections.