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通过尾纤维突变工程菌体宿主范围和抑制细菌抵抗力
Kevin Yehl1, Sébastien Lemire1, Andrew C Yang2
1Synthetic Biology Group, MIT Synthetic Biology Center, The Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; Research Laboratory of Electronics, MIT, Cambridge, MA 02139, USA.
Cell
|October 5, 2019
概括
在抗生素耐药性方面, 工程菌体尾部纤维创造了"菌体",可以防止细菌耐药性并抑制体外和体内生长.
科学领域:
- 微生物学
- 分子生物学
- 生物技术
背景情况:
- 抗生素耐药性是一个日益增长的全球健康威胁,
- 菌体 (菌体) 治疗是一种有前途的替代方案,但细菌对菌体的耐药性仍然是一个挑战.
- 工程菌素组件可能会克服或延迟细菌耐药性的发展.
研究的目的:
- 改造菌体尾部纤维以改变宿主范围并克服细菌的抵抗力.
- 开发一种高吞吐量方法来产生多样化,功能性的菌体变体.
- 在体外和体内评估工程菌体的疗效.
主要方法:
- 通过自然进化和结构建模在T3菌体尾部纤维蛋白中确定宿主范围确定区域 (HRDR).
- 采用位点定向的突变生成来基因工程HRDRs,创造合成的"菌体".
- 在小鼠模型中评估体宿主范围,细菌生长抑制,耐药性预防.
主要成果:
- 在HRDR中发生的突变成功地改变了菌体宿主范围.
- 通过预防耐药性,工程菌体在体外长期抑制了细菌的生长.
- 菌体在体内具有功能,在小鼠感染模型中显示有效性.
结论:
- 菌体尾纤维HRDR的基因工程是一种有效的策略,可以制造出强大的抗菌剂.
- 这种方法产生"菌体",可以减缓或阻止细菌耐药性的发展.
- 该方法有可能开发下一代抗菌药物和其他病毒支架应用.
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