一种人工智能设计的抗体工程益生菌疗法,向乌瑞斯,用于对抗小鼠的Helicobacter pylori感染
Feiliang Zhong1, Xintong Liu1, Xuefang Wang1
1Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
一种人工智能设计的针对Helicobacter pylori (Hp) 尿酶的益生菌显示出对抗抗生素耐药性感染的承诺. 这种新的策略显著减少了Hp的殖民,并促进了粘膜的修复,提供了一种对微生物群友好的治疗方法.
科学领域:
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
- 生物工程是生物工程.
背景情况:
- 杆菌 (Hp) 感染影响全球超过50%的人口,并且对抗生素的耐药性越来越强.
- 尿素是HP的关键毒性因子,使其成为治疗干预的关键目标.
研究的目的:
- 开发一种人工智能设计的益生菌战略,针对hp尿酶克服抗生素耐药性.
- 为了评估由益生菌细菌传递的工程单域抗体在减少Hp殖民和促进胃粘膜愈合方面的有效性.
主要方法:
- 针对Hp尿酶的人性化单域抗体 (UreBAb) 的AI指导工程,包括结构建模 (AlphaFold2) 和分子对接.
- 使用机器学习工具 (mCSA-AB,I-Mutant,FoldX) 来生成和选抗体变体.
- 通过工程Escherichia coli Nissle 1917 (EcN) 益生菌输送抗体变体 (I107W),并评估其在HP感染的小鼠模型中的有效性.
主要成果:
- 突变I107W抗体实现了65.6%的尿酶抑制,比野生型抗体显著改善.
- 表达I107W的工程EcN显著减少了超过4log10 CFU (治疗) 和3log10 CFU (预防) 的胃HP殖民 (p <0.001和p <0.05).
- I107W抗体治疗促进了增强的粘膜修复,并保持了稳定的肠道微生物群多样性.
结论:
- 人工智能引导的益生菌工程提供了一个强大的策略来对抗抗生素耐药的Helicobacter pylori.
- 由EcN提供的工程I107W抗体有效降低Hp负担并促进粘膜愈合.
- 这种方法为管理HP感染提供了一个有希望的,对微生物群友好的替代方案.
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