基于ESKAPE细菌的β-乳酸抗生素耐药性的分子基础 E. faecium 素结合蛋白 PBP5 PBP5
Yamanappa Hunashal1, Ganesan Senthil Kumar1,2, Meng S Choy1
1Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, CT, USA.
Nature communications
|July 17, 2023
概括
青素结合蛋白 (PBPs) 对于细菌细胞壁至关重要,并且是β-lactam抗生素的目标. 在Enterococcus faecium中,特定的PBP5变异增加了动态,增强了抗生素分解,并赋予了耐药性.
科学领域:
- 微生物学 微生物学
- 生物化学 生物化学
- 结构生物学 结构生物学
背景情况:
- 青素结合蛋白 (PBPs) 对于细菌细胞壁的合成至关重要.
- PBPs是β-乳酸抗生素的主要点.
- 菌体 (Enterococcus faecium) 呈现出高水平的β-乳酸盐耐药性,通常与PBP5表达和变体有关.
研究的目的:
- 阐明Enterococcus faecium中PBP5介导的β-乳酸盐耐药性的分子机制.
- 通过生物分子NMR光谱学研究PBP5变体的结构和动态特性.
主要方法:
- 生物分子NMR光谱学被用来研究PBP5,一个超过70kDa的蛋白质.
- 分析的重点是单独和与乙酶抑制剂复合的PBP5变体的动态.
- 测量了不同PBP5变体的酶水解速率.
主要成果:
- 与野生型相比,耐药的PBP5变种显示出显著增加的分子动力学.
- 在自由状态和在形成乙酶复合体时都观察到增强的动力学.
- 变种表现出增强的乙酶水解率,表明抗生素周转率更快.
结论:
- 在PBP5变体中,减少侧链的体积和扩展的表面环带来了更大的动力.
- 这些动态变化促进了乙酶的水解,从而导致β-乳酸盐耐药性.
- 这些发现为临床E. faecium PBP5变体和潜在的其他PBP的耐药性提供了分子基础.
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