Harnessing the power of ferulic acid as a dual-action strategy against biofilm-forming extensively drug-resistant Acinetobacter baumannii isolated from cancer patients: in vitro and in vivo study

Abstract

The increasing prevalence of extensively drug-resistant Acinetobacter baumannii (XDRAb), particularly biofilm-producing strains, poses a significant threat to clinical management, especially in immunocompromised patients. This study investigates the potential of ferulic acid (FA) as a dual-function therapeutic agent with antibacterial and antibiofilm capabilities. A total of 34 XDRAb isolates were obtained from cancer patients, and FA’s activity was assessed using a range of in vitro assays and in vivo neutropenic rat wound infection model. FA exhibited marked antimicrobial activity against XDRAb (MIC: 512 to 1024 µg/mL). At su-binhibitory concentrations (¼ and ½ MIC), FA significantly inhibited biofilm formation by 43.2 and 67.6% and disrupted established biofilms by 29.4 and 54.8% (p < 0.05), respectively. Consistent with these effects, FA also reduced cell surface hydrophobicity and exopolysaccharide production in XDRAb isolates. Microscopic imaging via light, scanning electron, and confocal laser scanning microscopy corroborated these findings, revealing substantial structural degradation of biofilms upon treatment. At the molecular level, FA significantly downregulated (p < 0.05) the key biofilm-associated genes (abaI, bfmR, bap, csuE, and pgaB), as quantified by RT-qPCR. In vivo, FA significantly enhanced the wound healing rates (approximately 82%, p < 0.05) and reduced the wound bacterial burden (p < 0.05). Histopathological examination showed near-complete restoration of epithelium architecture seven days post-treatment in the FA-treated group. Collectively, this study demonstrates that FA exerts combined antimicrobial and antibiofilm activities against XDRAb in preclinical models. Our findings indicate that FA interferes with multiple stages of biofilm development while exhibiting antibacterial activity at higher concentrations. These results support further investigation of FA as antibiofilm or adjunct candidate, particularly for localized biofilm-associated XDRAb infections.