由 metionin 驱动的甲基化修饰克服了通过等离子体介导的高水平tigecycline 耐药性
Dan Fang1, Tianqi Xu1, Fulei Li1
1Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
Nature communications
|January 6, 2025
概括
通过表观遗传修饰,L-甲 (Met) 通过促进药物积累和减少tet(X4) 基因表达,使细菌对tigecycline重新敏感. 这种代谢策略克服了多抗药性病原体中的tigecycline耐药性.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 由等离子体传播的tet(X) 基因介导的tigecycline耐药性是一个日益增长的临床威胁.
- 需要新的策略来对抗多药耐药性病原体,这些病原体对tigecycline等最后手段抗生素也具有耐药性.
研究的目的:
- 为了研究对tigecycline耐药和敏感细菌之间的代谢差异.
- 探索L-氨酸 (Met) 作为一种克服tigecycline耐药性的潜在药物.
主要方法:
- 在tigecycline压力下对tet(X) 阳性和阴性大肠杆菌进行比较的代谢分析.
- 评估外源L-甲氨酸对tigecycline in vitro和in vivo疗效的影响.
- 涉及质子动力,S-adenosyl-L-methionine水平和tet(X4) 促进体的DNA甲基化 (5mC) 的机制研究.
主要成果:
- 氨酸和氨酸的新陈代谢在阳性细菌中被降低.
- 外源性L-甲氨酸对tigecycline重新敏感化X阳性病原体.
- 通过调高质子动力和促进DNA甲基化,L-甲氨酸增强了细胞内tigecycline积累,并减少了tet(X4) 表达.
结论:
- 通过向代谢和表观遗传途径,L-氨酸增强了对抗耐药菌株的tigecycline疗效.
- 这种方法提供了一种有前途的治疗策略,用于对抗由大肠杆菌和K. pneumoniae引起的感染中的tigecycline耐药性.
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