双组分调节剂BaeSR的突变调解了 cefiderocol 耐药性,并增强了 Acinetobacter baumannii 的毒性
Xiaochen Liu1,2,3, Yunjie Chang1,4,5, Qingye Xu6
1Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang, China.
mSystems
|June 22, 2023
概括
BaeS-BaeR 系统中的突变通过增加排泄表达来降低 Acinetobacter baumannii 中的 cefiderocol 敏感性. 这个系统还影响细菌的毒性和生物膜的形成,这对于理解多药耐药性感染至关重要.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 抗微生物耐药性 抗微生物耐药性
背景情况:
- 宝曼尼菌 (Acinetobacter baumannii) 是一种具有挑战性的病原体,治疗选择有限.
- 塞菲德罗科尔在体外表现出对抗耐药菌株的活性,但对耐药性机制的了解很少.
研究的目的:
- 在Acinetobacter baumannii中研究 cefiderocol耐药性机制.
- 阐明 BaeS-BaeR 两组分系统在 cefiderocol 耐药性和毒性中的作用.
主要方法:
- 在体外进化实验中试验产生耐药菌株.
- 基因组工程引入特定突变.
- 转录组分析以确定基因表达变化.
- 盖勒里亚梅隆氏菌感染模型用于评估毒性.
主要成果:
- 对Cefiderocol耐药菌株在BaeS-BaeR中获得了突变.
- 设计的 BaeS/BaeR 突变增加了 cefiderocol MICs 和调高了排泄 (MFS, MacAB-TolC).
- BaeSR 突变也影响了 csu 和 paa 操作子,影响了运动性,生物膜形成和毒性.
结论:
- 在BaeS-BaeR中发生的突变通过排水的上调来降低塞菲德罗尔的敏感性.
- BaeSR 调节生物膜的形成,运动和毒性,影响 Acinetobacter baumannii 的致病性.
- 了解 BaeSR 的作用对于对抗 MDRAB 中的 cefiderocol 耐药性至关重要.
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