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大黄素单独或与氨苄西林联合应用对耐甲氧西林金黄色葡萄球菌的抗生物膜作用

Antibiofilm efficacy of emodin alone or combined with ampicillin against methicillin-resistant Staphylococcus aureus.

作者信息

Zhao Maoying, Chen Fuhong, Yang Wei, Yan Tao, Chen Qi

机构信息

Department of Clinical Laboratory, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310000, China.

出版信息

Sci Rep. 2025 Jul 1;15(1):21904. doi: 10.1038/s41598-025-06800-5.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is recognized as a significant global health concern. The development of resistance to a broad spectrum of antibiotics, particularly following biofilm formation, renders conventional therapeutic options for MRSA ineffective. Three MRSA clinical isolates were examined in vitro to assess their biofilm-forming capacity and the disruptive effects on pre-established biofilm (via crystal violet staining and scanning electron microscopy), and quantify extracellular DNA (eDNA) release after exposed to emodin alone or in combination with ampicillin. In addition, real-time PCR was employed to investigate the impact of emodin on the expression of biofilm-related genes in MRSA biofilms. The inhibitory effect of emodin on biofilm formation and disruption was observed in a dose dependent manner. The antagonistic activity of emodin in combination with ampicillin against MRSA biofilms was confirmed through adhesion assays. Real-time PCR analysis revealed that emodin, either alone or in combination with ampicillin, effectively downregulated the transcriptional levels of the biofilm-related genes fnbpB, clfA and atlA, but not icaA. In addition, drug treatment resulted in a significant reduction in eDNA release and protein contain in EPS (extracellular polymeric substances), which corresponded to the markedly decreased transcript level of atlA and fnbpB, respectively. These observations suggest that emodin, either alone or in combination with ampicillin, holds potential as a therapeutic approach for MRSA biofilm-related infections.

摘要

耐甲氧西林金黄色葡萄球菌(MRSA)被认为是一个重大的全球健康问题。对多种抗生素产生耐药性,尤其是在形成生物膜之后,使得针对MRSA的传统治疗方案无效。对三株MRSA临床分离株进行了体外研究,以评估它们形成生物膜的能力以及对预先形成的生物膜的破坏作用(通过结晶紫染色和扫描电子显微镜),并量化单独暴露于大黄素或与氨苄西林联合暴露后细胞外DNA(eDNA)的释放。此外,采用实时定量PCR研究大黄素对MRSA生物膜中生物膜相关基因表达的影响。观察到大黄素对生物膜形成和破坏的抑制作用呈剂量依赖性。通过黏附试验证实了大黄素与氨苄西林联合对MRSA生物膜的拮抗活性。实时定量PCR分析表明,大黄素单独或与氨苄西林联合使用均能有效下调生物膜相关基因fnbpB、clfA和atlA的转录水平,但对icaA无影响。此外,药物处理导致eDNA释放和胞外聚合物(EPS)中蛋白质含量显著降低,这分别对应于atlA和fnbpB转录水平的明显下降。这些观察结果表明,大黄素单独或与氨苄西林联合使用,有望成为治疗MRSA生物膜相关感染的一种方法。

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