Department of Urology Surgery Center, The People's Hospital of Xinjiang Uyghur Autonomous Region, Urumqi 830002, PR China.
Department of Urology Surgery Center, The People's Hospital of Xinjiang Uyghur Autonomous Region, Urumqi 830002, PR China; School of Biological and Pharmaceutical Sciences, Shaanxi University of Science & Technology, Xi'an 710021, PR China; Key Laboratory for Antiviral and Antimicrobial-Resistant Bacteria Research of Xi'an, Xi'an 710021, PR China.
Phytomedicine. 2024 Dec;135:156038. doi: 10.1016/j.phymed.2024.156038. Epub 2024 Sep 13.
Antibiotic resistance complicates infection treatments. Natural products, such as phenylethanoid glycosides, including forsythoside B (FB), are gaining attention in clinical use as alternative treatments, either alone or in combination with antibiotics.
To investigate the antibacterial effects and mechanisms of FB alone and in combination with antibiotics against Acinetobacter baumannii and Pseudomonas aeruginosa.
To elucidate the underlying antibacterial mechanism of FB, we assessed intracellular ATP concentration, pH levels, membrane potential, and cell membrane integrity. We also observed bacterial morphology and conducted biofilms eradication assay. FB toxicity was evaluated using the cell counting kit-8 assay. The in vivo pharmacodynamics of FB was explored using a P. aeruginosa systemic infection mouse model. The study also examined the potential synergistic effects of FB with commonly used antibiotics by the checkerboard dilution method and time-kill assay.
The findings indicate that the mechanism of antibacterial activity of FB is through the disruption of bacterial cell membranes, thereby increasing cell membrane permeability, particularly in gram-negative bacteria. Synergistic effects of FB combined with meropenem were demonstrated against resistant strains. FB demonstrated low toxicity in both in vitro and in vivo models, supporting its safety and efficacy for use alone or as an antibiotic adjuvant.
FB expands the antibacterial spectrum and enhances the effectiveness of existing antibiotics against resistant bacterial strains, making it a promising adjuvant for treating gram-negative bacterial infections. This study highlights the potential of FB in combating antibiotic resistance and suggests further research into its mechanisms and drug development applications. It provides a framework for studying the interaction between natural products and microorganisms, revealing new biological mechanisms.
抗生素耐药性使感染治疗变得复杂。天然产物，如苯乙醇苷类，包括连翘酯苷 B（FB），作为替代治疗药物，无论是单独使用还是与抗生素联合使用，都越来越受到临床关注。
研究 FB 单独和联合抗生素对鲍曼不动杆菌和铜绿假单胞菌的抗菌作用和机制。
为了阐明 FB 的潜在抗菌机制，我们评估了细胞内 ATP 浓度、pH 值、膜电位和细胞膜完整性。我们还观察了细菌形态并进行了生物膜清除试验。使用细胞计数试剂盒-8 法评估 FB 毒性。使用铜绿假单胞菌全身感染小鼠模型研究了 FB 的体内药效动力学。该研究还通过棋盘稀释法和时间杀伤试验检查了 FB 与常用抗生素联合使用的潜在协同作用。
研究结果表明，FB 的抗菌活性机制是通过破坏细菌细胞膜，从而增加细胞膜通透性，特别是在革兰氏阴性菌中。FB 与美罗培南联合对耐药株表现出协同作用。FB 在体外和体内模型中均显示出低毒性，支持其单独使用或作为抗生素佐剂的安全性和有效性。
FB 扩大了抗菌谱，并增强了现有抗生素对耐药菌株的疗效，使其成为治疗革兰氏阴性菌感染的有前途的佐剂。本研究强调了 FB 对抗生素耐药性的潜力，并提出了进一步研究其机制和药物开发应用的建议。它为研究天然产物与微生物之间的相互作用提供了框架，揭示了新的生物学机制。
