来自Streptococcus parauberis的细胞外囊泡促进了LL37的高效传递,增强了抗菌活性
E H T Thulshan Jayathilaka1, Mawallage Kankanamge Hasitha Madhawa Dias1, Chamilani Nikapitiya1
1College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungnam National University, Yuseong-gu, Daejeon 34134, Republic of Korea.
Fish & shellfish immunology
|November 8, 2025
概括
携带抗菌LL37的细菌细胞外囊泡 (BEV) 显示出对Streptococcus parauberis感染的增强疗效. 这些工程囊泡 (SpEVs-LL37) 显示出改善的抗菌活性,降低毒性,并在体内增强免疫反应,突显了它们的治疗潜力.
科学领域:
- 生物技术是生物技术.
- 微生物学 微生物学
- 药物运输 药物运输 药物运输
背景情况:
- 细菌细胞外囊泡 (BEV) 是抗菌 (AMP) 等生物活性分子的有希望的载体.
- LL37是一种人体甲基胺衍生的AMP,具有抗菌性质,但需要有效的输送系统.
- 杆菌 (Streptococcus parauberis) 是一种病原体,需要新的治疗策略.
研究的目的:
- 将LL37封装到Streptococcus parauberis衍生的BEV (SpEV) 中,以增强药物输送.
- 评估LL37装载SpEVs (SpEVs-LL37) 的物理化学特性,细胞毒性,抗菌活性和体内疗效.
- 为了研究SpEVs-LL37对S. parauberis感染的治疗潜力.
主要方法:
- 通过共同化,LL37被封装到SpEV中.
- 使用场发射电子显微镜和纳米粒子追踪分析 (NTA) 的物理化学表征.
- 试验室试验包括细胞毒性,细胞内化,最小抑制度 (MIC),最小杀菌度 (MBC),时间杀伤动力学,细菌活力,膜透性和反应性氧物种 (ROS) 生成.
- 在斑马鱼体内研究评估了免疫基因表达和抗病能力.
主要成果:
- SpEVs-LL37实现了28.5%的封装效率和57%的负载能力,保持了囊泡形态和负面表面电荷.
- 与单独LL37相比,SPEVs-LL37表现出较低的细胞毒性和类似的细胞吸收.
- 与单独使用LL37 (MIC: 10 μg/mL,MBC: 25 μg/mL) 相比,SpEVs-LL37对S. parauberis (MIC: 5 μg/mL,MBC: 10 μg/mL) 的抗菌活性更强.
- 通过SpEVs-LL37.37,观察到增强的细菌膜损伤和ROS生成.
- 在体内,SpEVs-LL37提高了免疫基因的调节,并使斑马鱼具有更强的抗病能力.
结论:
- 此外,SpEVs作为LL37的有效载体,增强其抗菌性能.
- 与单独使用LL37相比,SPEVs-LL37提供了更安全,更有效的治疗选择.
- 这些发现支持SpEVs-LL37的发展,作为治疗S. parauberis和其他感染的新平台.
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