在Escherichia coli和Nissle 1917中设计一种新的益生菌工具包,用于检测和缓解肠道炎症疾病
Nathalie Weibel1, Martina Curcio1, Atilla Schreiber1
1University of Zürich, Campus Irchel Winterthurerstrasse 190, 8057 Zürich, Switzerland.
ACS synthetic biology
|August 8, 2024
概括
工程细菌为炎症性肠病 (IBD) 提供向治疗. 这种新型系统使用益生菌细菌分泌抗TNFα纳米体,为慢性肠道炎症提供了潜在的新疗法.
科学领域:
- 合成生物学 合成生物学
- 胃肠病学 胃肠病学
- 细菌工程是一种细菌工程.
背景情况:
- 炎症性肠病 (IBD) 由于慢性肠道炎症,缺乏治愈方法和有限的治疗方法带来全身副作用,因此具有重大临床挑战.
- 目前对IBD的治疗策略往往缺乏特异性,并可能导致不良副作用.
研究的目的:
- 为潜在的炎症性肠病 (IBD) 治疗设计一个针对特定目标的益生菌系统.
- 开发Escherichia coli* Nissle 1917 (EcN) 中的一个模块化系统,用于检测炎症和输送治疗载荷.
主要方法:
- 工程 *Escherichia coli* Nissle 1917 (EcN) 配有氧化 (NO) 传感器 (NorR),1型血解素分泌系统和抗TNFα纳米体.
- 评估了系统对NO的反应,并使用酶相关免疫吸收试验 (ELISA) 和体外试验来表征纳米体的功能.
- 开发了一个数学框架来建模工程益生菌系统的关键参数.
主要成果:
- 设计的EcN系统对氧化 (NO) 的反应依赖于度.
- 功能性抗TNFα纳米体的分泌成功,其结合亲和力与阿达利穆马布相似.
- 血清素分泌系统在EcN中首次被描述,证明了其在蛋白质选和净化方面的实用性.
结论:
- 开发的纳米体库扩大了EcN在IBD治疗中的治疗潜力.
- 工程化益生菌系统为在炎症条件下有针对性地输送生物制剂提供了一个新的平台.
- 这项研究提供了一个合成生物学框架和数学模型,用于推进工程益生菌疗法.
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