Unlocking p-coumaric acid's potential against biofilm-forming extensively drug-resistant Acinetobacter baumannii: in vitro and in vivo study.

backgroundThe global rise of extensively drug-resistant Acinetobacter baumannii, particularly biofilm-forming strains, has drastically limited treatment options and created an urgent need for novel therapies to restore antibiotic efficacy. This study explored p-coumaric acid (p-CA) as a potential dual-action agent to combat biofilm-associated XDR Acinetobacter baumannii infections and restore imipenem efficacy.

methodsAmong 100 clinical Acinetobacter baumannii isolates, 32 were identified as XDR and exhibited resistance to imipenem. The antimicrobial and antibiofilm efficacy of p-CA was systematically evaluated through comprehensive in vitro assays and an in vivo rat infection model. Minimum inhibitory concentrations were determined via the broth microdilution method, and the potential modulation effect on imipenem efficacy was investigated. To assess biofilm inhibition and disruption, quantitative analyses were performed using the crystal violet staining technique, complemented by evaluating its impact on the bacterial cell surface hydrophobicity and exopolysaccharide production. Biofilm structural changes were analyzed via light, scanning electron, and confocal laser scanning microscopy. Additionally, the expression levels of key biofilm-associated genes were quantified via quantitative reverse transcription PCR.

resultsThe p-CA exhibited potent antimicrobial activity against the tested isolates (MIC: 512 µg/mL) and synergized with imipenem, reducing its MIC by 512-fold. At subinhibitory concentrations (¼-½ MIC), it inhibited biofilm formation (66.2-80.5%, p < 0.05) and disrupted pre-formed biofilms (45.8-71.3%, p < 0.05), likely via altered cell surface hydrophobicity and reduced EPS production. Microscopic imaging corroborated these findings, revealing substantial structural degradation of biofilms upon treatment. At the molecular level, p-CA significantly downregulated (p < 0.05) the key biofilm-associated genes (abaI, bfmR, bap, csuE, and pgaB), as quantified by RT-qPCR. In vivo, the p-CA/imipenem combination significantly enhanced the survival rates (100%, p < 0.05) and reduced the lung bacterial burden (p < 0.001). Histopathological examination showed near-complete restoration of alveolar architecture by 72 h post-treatment in the combination therapy group.

conclusionThese findings position p-CA as a promising dual-action adjuvant against XDR Acinetobacer baumannii infections, particularly in biofilm-associated contexts. It combines direct antimicrobial activity, biofilm disruption, and synergy with imipenem to address critical treatment gaps.