碳酸无水酶抑制作为在肠球菌中抗生素协同作用的目标
Gayatri Shankar Chilambi1, Yu-Hao Wang1, Nathan R Wallace1
1Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Microbiology spectrum
|June 1, 2023
概括
阿尔法碳酸胺酶 (α-CA) 的突变使得Enterococcus faecalis通过增加药物吸收,对 gentamicin高度敏感. 经FDA批准的α-CA抑制剂可以增强 gentamicin 的作用.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- Enterococcus faecalis是医院相关感染的重要原因,经常表现出多种药物耐药性.
- 开发新的治疗策略对于治疗耐药性肠球菌感染至关重要.
研究的目的:
- 为了研究α-碳酸无水素酶 (α-CA) 突变对E. faecalis. gentamicin的过敏性所带来的机制.
- 探索α-CA抑制剂作为对肠球菌感染 gentamicin 治疗的辅助剂的潜力.
主要方法:
- 隔离和表征一种 gentamicin-hypersusceptible E. faecalis 菌株,该菌株具有 α-CA 突变.
- 测量细胞内胺素吸收,质子运动力 (PMF) 和膜透性.
- 评估α-CA抑制剂阿扎胺对 جنت米辛最小抑制度 (MIC) 的影响.
主要成果:
- 与野生型菌株相比,α-CA突变菌株表现出显著增加的细胞内 gentamicin 积累.
- 在α-CA突变体中观察到增加的PMF和改变的膜组成,与增强的透性相一致.
- 乙胺在野生型E. faecalis菌株中降低了珍塔素MIC,但在α-CA突变菌中没有.
结论:
- α-CA 干扰通过增加 PMF 和膜透性来增强 E. faecalis 中的 gentamicin 吸收.
- 美国食品和药物管理局批准的α-CA抑制剂可以使E. faecalis对健美素敏感,这表明可能出现新的组合疗法.
- 向α-CA是克服肠球菌感染中氨基糖化物耐药性的有希望的策略.
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