跨RND多药物排放的基因组群的形态塑性及其对基质特异性的影响
Mariya Lazarova1, Thomas Eicher1, Clara Börnsen2
1Institute of Biochemistry, Goethe-University Frankfurt, Frankfurt, Germany.
Nature communications
|November 26, 2025
概括
通过了解耐药结节和细胞分裂 (RND) 排泄如何结合抗生素,可以减少细菌的多药性耐药性. 一个单一的氨基酸变化改变了的功能和形状,影响了抗生素耐药性.
科学领域:
- 微生物学 微生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 抗生素排放对于格拉姆阴性细菌的多药耐药性至关重要.
- 抗性结结和细胞分裂 (RND) 超级家族蛋白质形成细胞外系统,使其对各种抗生素产生抗性.
研究的目的:
- 调查RND排水中保存的结合性口袋残留物的作用.
- 了解这些残留物中的变化如何影响抗生素耐药性表型和结构状态.
主要方法:
- 对RND蛋白质的遗传学分析.
- 局部定向的突变发生,以转移保存的残留物.
- 对抗生素耐药性的表型分析.
- 单粒子冷电子显微镜 (cryo-EM) 用于确定AcrB和OqxB的apo状态.
主要成果:
- 确定了两个不同的RND蛋白质的基因组群,其中保留了结合口袋残留物.
- 在集群之间转移单个保存残留物,通过修改结合口袋特性和构造平衡,改变了耐药性表型.
- 代表两个群体的AcrB和OqxB表现出不同的apo状态,表明不同的基质结合机制.
- 在RND中保持了符合性可塑性,并有助于阻力多样化.
结论:
- 一个单一的保存残留物显著影响RND排水功能和基质结合.
- RND的不同状态表明了抗生素识别和运输的不同机制.
- RND的形状可塑性在遗传学上得到保护,并推动了多药耐药性的演变.
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