一种以自然为导向的抗生素, 针对多种耐药性病原体
Zongqiang Wang1, Bimal Koirala1, Yozen Hernandez1
1Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, NY, USA.
Nature
|January 6, 2022
概括
一种新的抗生素, 马可拉辛, 这种来自自然的化合物对危险的病原体如Acinetobacter baumannii有效,
科学领域:
- 微生物学
- 药物发现
- 基因组学
背景情况:
- 格拉姆阴性细菌的抗生素耐药性是一个日益严重的全球健康危机.
- 科里斯是一种关键的最后避险抗生素,
- mcr-1 基因的传播显著威胁着素的疗效.
研究的目的:
- 调查自然存在的胆固醇原体的溶液对mcr-1介导的耐药性.
- 识别和合成有效对抗抗菌素的新化合物.
- 开发用于广泛抗药性格拉姆阴性感染的新疗法.
主要方法:
- 细菌基因组的生物信息分析以确定相关的生物合成基因群.
- 一个预测的胆固醇原体的化学合成, macolacin.
- 在体外和体内对格兰氏阴性病原体进行检测,包括具有mcr-1和内在耐药性的病原体.
- 在小鼠感染模型中评估macolacin模拟物.
主要成果:
- 一种新型的胆固醇同源,马可拉,被发现并合成.
- 马可拉辛对表达mcr-1的格兰负病原体表现出活性.
- 这种化合物对内在耐菌素的细菌有效,包括Acinetobacter baumannii和Neisseria gonorrhoeae.
- 在小鼠模型中,一种macolacin类型对具有广泛耐药性,耐素的Acinetobacter baumannii显示出有效性.
结论:
- 自然存在的胆固醇原体可以解决新出现的抗生素耐药性问题.
- 马可拉是一种有前途的,自然启发的治疗方法,用于对抗抗菌素抗性格兰氏阴性感染.
- 这些发现为克服抗药性细菌带来的重大威胁提供了潜在的策略.
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