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, Germany.
bioRxiv : the preprint server for biology
|November 28, 2024
概括
格拉姆阴性细菌的多药耐药性是由抗生素排泄驱动的. 这些抵抗结节和细胞分裂 (RND) 蛋白中的单个氨基酸变化显著改变了耐药性和功能.
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:
- 通过抗性结节和细胞分裂 (RND) 超级的抗生素排放是格兰氏阴性细菌多药性耐药性的主要机制.
- 这些作为跨越细菌细胞外的复杂系统的一部分,使其对广泛的抗生素产生耐药性.
研究的目的:
- 调查RND排水的结合口袋中的保存残留物的作用.
- 了解RND的结构变化如何影响基质特异性和耐药性.
- 探索RND进化中的形状异质性的遗传学保存.
主要方法:
- 遗传学分析以确定RND蛋白质的集群与保存的结合口袋残留物.
- 代表性RND (K. pneumoniae OqxB和E. coli AcrB) 的生物化学特征.
- 位点定向突变发生,以研究单一残留物替代对耐药性和形状的影响.
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OqxB和AcrB之间替换单个保存残留物改变了对结构上不同的抗生素的耐药性.
- 这种替换影响了绑定口袋架构和运输周期的构造状态平衡.
- AcrB和OqxB表现出不同的阿波状态,表明不同的基质结合机制,并有助于各种基质偏好.
结论:
- 一个单一的保存残留物在确定RND排泄的耐药性和基质特异性方面发挥着至关重要的作用.
- RND集群之间的形态异质性是基因遗传学上保存的,可能有助于多种药物耐药性表型的多样化.
- 了解这些结构和功能上的差异对于制定打击抗生素耐药性的战略至关重要.
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