Butenolide synergises with vancomycin to eradicate pre-formed biofilm of Staphylococcus aureus by interfering with energy-associated metabolism

作者：Di Hu, Jinyou Liang, Jing Yan, Zhi-Wen Ma, Hailin Li, Ying Xu, Yu Zhang, Qi Yin · 发表于：Biofouling · 年份：2025 · DOI：10.1080/08927014.2025.2531136 · 被引用次数：2 · 研究领域：Bacterial biofilms and quorum sensing、Antimicrobial Resistance in Staphylococcus、Antifungal resistance and susceptibility

Bacterial biofilms significantly contribute to persistent infections and the emergence of drug resistance of Staphylococcus aureus. Integrating conventional antibiotics with antibiofilm agents represents a promising strategy for combating biofilm-associated infections. This study systematically investigated the antibiofilm activity and underlying mechanisms of butenolide (BU) against methicillin-resistant S. aureus (MRSA), with a focus on the synergistic effects between BU and vancomycin (VAN). BU exhibited dual antibiofilm activities by efficiently preventing biofilm formation and eradicating established biofilms. Phenotypic characterisation revealed that 200 μg/mL of BU suppressed extracellular DNA production and autoaggregation of MRSA, leading to a significant reduction in biofilm thickness, biovolume, and coverage by up to 30%, 98%, and 96%, respectively. Transcriptome and quantitative-PCR analyses showed that BU treatment downregulated the expression of genes involved in energy metabolism. Notably, BU exhibited promising synergistic and additive effects with VAN in eradicating pre-formed biofilms, achieving synergy or additivity in five out of six S. aureus clinical strains tested, with a minimal fractional inhibitory concentration index as low as 0.375. These results highlight the potential of BU as an effective antibiofilm agent for preventing S. aureus-related infections.