通过DNA Aptamers的介导,抑制了致病性Erm42酶,该酶参与了抗微生物耐药性
Leena Laxmikant Badgujar1, Damini Sahu1, Ruchi Anand1
1Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400076, Maharashtra, India.
ACS infectious diseases
|December 29, 2025
概括
研究人员开发了针对Erm42酶的DNA吸收剂,这是抗菌素耐药性的关键因素. 这些胺体表现出高亲和力并抑制Erm42,为抗药性病原体提供了潜在的新策略.
科学领域:
- 分子生物学分子生物学
- 生物化学 生化学
- 药物发现 药物发现 药物发现
背景情况:
- 抗菌素耐药性 (AMR) 是由病原体耐药性机制驱动的日益增长的威胁.
- 抗红素的甲基转移酶 (Erm) 酶通过修改核糖体RNA (rRNA) 来产生对多种抗生素的耐药性.
- 缺少Erm酶,特别是Erm42的特定抑制剂.
研究的目的:
- 发现和表征高亲和度DNA吸收体,以致病原Erm42甲基转移酶为目标.
- 为了评估这些阿普坦体对Erm42-介导的rRNA甲基化的抑制潜力.
- 开发基于DNA体的新型工具,用于对抗AMR.
主要方法:
- 实验室内选择 (SELEX) 用于识别针对Erm42.2的DNA吸收体.
- 使用诸如表面等离子体共振 (SPR) 或类似的技术来评估结合亲和力.
- 通过测量rRNA甲基化减少,证实了抑制活性.
- 用DNase I足迹测试来描述aptamer结合和工程师截断的版本.
主要成果:
- 两种高亲和度DNA吸收体,Apt-E1和Apt-E2,被确定为对Erm42.2具有纳米分子结合亲和度.
- 这些胺酶有效抑制了Erm42.4的甲基转移酶活性.
- 工程截断的阿普坦体表现出与Erm42.2相似的结合性和增强的特异性.
- 对其它甲基转移酶和DNA结合蛋白的特异性进行了验证.
结论:
- 开发了针对Erm42的新型DNA吸收剂.
- 这些胺体代表了一种有前途的新策略,用于抑制Erm介导的AMR.
- 这些发现为开发基于aptamer的治疗方法和诊断方法铺平了道路,以对抗多药耐药病原体.
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