College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Heilongjiang Provincial Key Laboratory of Zoonosis, Harbin 150030, China.
Molecules. 2023 Nov 16;28(22):7630. doi: 10.3390/molecules28227630.
Enterococci resistance is increasing sharply, which poses a serious threat to public health. Rhamnolipids are a kind of amphiphilic compound used for its bioactivities, while the combination of nontraditional drugs to restore linezolid activity is an attractive strategy to treat infections caused by these pathogens. This study aimed to investigate the activity of linezolid in combination with the rhamnolipids against . Here, we determined that the rhamnolipids could enhance the efficacy of linezolid against enterococci infections by a checkerboard MIC assay, a time-kill assay, a combined disk test, an anti-biofilm assay, molecular simulation dynamics, and mouse infection models. We identified that the combination of rhamnolipids and linezolid restored the linezolid sensitivity. Anti-biofilm experiments show that our new scheme can effectively inhibit biofilm generation. The mouse infection model demonstrated that the combination therapy significantly reduced the bacterial load in the feces, colons, and kidneys following subcutaneous administration. This study showed that rhamnolipids could play a synergistic role with linezolid against . Our combined agents could be appealing candidates for developing new combinatorial agents to restore antibiotic efficacy in the treatment of linezolid-resistant infections.
肠球菌的耐药性正在急剧上升，这对公众健康构成了严重威胁。鼠李糖脂是一种具有生物活性的两亲性化合物，而将非传统药物联合使用以恢复利奈唑胺的活性是治疗这些病原体引起的感染的一种有吸引力的策略。本研究旨在研究利奈唑胺与鼠李糖脂联合使用对肠球菌的活性。在这里，我们通过棋盘微量稀释法、时间杀伤试验、联合药敏纸片试验、抗生物膜试验、分子模拟动力学和小鼠感染模型确定了鼠李糖脂可以增强利奈唑胺对肠球菌感染的疗效。我们发现，鼠李糖脂和利奈唑胺的联合使用恢复了利奈唑胺的敏感性。抗生物膜实验表明，我们的新方案可以有效抑制生物膜的生成。小鼠感染模型表明，联合治疗可显著减少皮下给药后粪便、结肠和肾脏中的细菌负荷。本研究表明，鼠李糖脂可以与利奈唑胺发挥协同作用，抑制肠球菌。我们的联合制剂可能是开发新的联合制剂的有吸引力的候选药物，以恢复治疗利奈唑胺耐药肠球菌感染的抗生素疗效。
