在Enterococcus faecalis中揭示了Ceftobiprole和高分子量 (HMM) 青素结合蛋白 (PBPs) 之间的关系
Paola Conti1,2, Lorenzo Mattia Lazzaro1, Fabio Longo1,3
1Department of Biomedical and Biotechnological Sciences (BIOMETEC), Section of Microbiology, University of Catania, 95123 Catania, Italy.
Antibiotics (Basel, Switzerland)
|January 22, 2024
概括
青素结合蛋白4 (PBP4) 是必要的,但不足以在Enterococcus faecalis.中产生抗的. 进一步的研究表明,PBP4可能与其他PBP合作,引起耐药性.
科学领域:
- 微生物学 微生物学
- 生物化学 生物化学
- 分子生物学分子生物学
背景情况:
- 青素结合蛋白4 (PBP4) 与Enterococcus faecalis.中的青素耐药性有关.
- 塞夫托比 (BPR) 是一种关键的治疗药物,但涉及PBP4的耐药性机制尚未完全理解.
- 青素耐药 - - 青素敏感 - - 青素耐药 - - 青素敏感 - - 青素不敏感 (PRAS/BPR-NS) E. faecalis菌株对治疗提出了挑战.
研究的目的:
- 对PRAS/BPR-NS E. faecalis. 的临床分离物中,研究 ceftobiprole (BPR) 和高分子量 (HMM) 低反应性青素结合蛋白 (PBPs) 之间的相互作用.
- 确定PBP4在 ceftobiprole耐药性中的作用.
- 探索涉及多个PBP的潜在合作抵抗机制.
主要方法:
- 竞争试验使用来自四种PRAS/BPR-NS E. faecalis菌株的净化膜蛋白进行.
- 光性青素 (Bocillin FL) 用于评估在存在或缺少 ceftobiprole 的情况下的PBP 乙化.
- 对各种PBP的托比罗的50%抑制度 (IC50) 通过分析光强度来计算.
主要成果:
- PBP4表现出较低的亲和力,并且在测试的菌株中没有显著的化.
- PBP1a和PBP1b对 ceftobiprole表现出类似的不敏感性.
- 其他PBP的IC50值为ceftobiprole的最小抑制度 (MIC) 的0.5倍至4倍.
- 在较高的 ceftobiprole 度下观察到PBP4 抑制的增加.
结论:
- 虽然PBP4是必不可少的,但不仅仅足以在E. faecalis中赋予 ceftobiprole耐药性.
- 这些发现挑战了目前关于肠球菌中头胞素耐药性的现有范式.
- 假设PBP4和至少一个双功能类APBP之间的合作相互作用是必要的,以便在托比的压力下合成丁糖和细菌生长.
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