在AcrB中功能上不同的突变是不同生活方式中抗生素耐药性的基础
Eleftheria Trampari1, Filippo Prischi2, Attilio V Vargiu3
1Quadram Institute Bioscience, Norwich Research Park, Norwich, Norfolk NR4 7UQ UK.
npj antimicrobials and resistance
|April 30, 2024
概括
沙门氏菌通过AcrB排泄的突变而发展出抗生素耐药性. 这些变化,R717L对亚齐思罗素和Q176K对西福胺,赋予了耐药性,并在全球范围内发现.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 抗生素耐药性是全球主要的健康威胁.
- 多种药物排放系统,如沙门氏菌中的AcrB,积极地从细菌细胞中抽出抗生素,从而促进耐药性.
- 了解耐药机制对于开发有效的治疗方法至关重要.
研究的目的:
- 在不同的生长条件下 (浮游生物与生物膜) 调查沙门氏菌对塞福他辛和亚齐菌素耐药性的演变.
- 为了确定负责赋予抗性的AcrB载体中的特定突变.
- 阐明这些突变赋予耐药性的独特机制.
主要方法:
- 在抗生素选择下的细菌生长 (浮游生物和生物膜).
- 基因测序以确定AcrB,ramR和envZ中的突变.
- 结构,遗传和表型分析以表征突变效应.
- 抗生素敏感性测试. 抗生素敏感性测试.
主要成果:
- 沙门氏菌在浮游生物和生物膜条件下对甲胺和亚齐胺产生了耐药性.
- 特定的AcrB替代物,R717L (对于亚齐思罗素) 和Q176K (对于塞福胺),被确定为耐药性的关键驱动因素.
- 这些替代,通常伴随着ramR或envZ的突变,导致临床耐药性和交叉耐药性.
- 结构分析显示,R717L降低了硬质障碍,而Q176K则增强了塞福胺的结合和识别.
结论:
- 独特的AcrB替代物通过独特的机制赋予了对不同抗生素的耐药性.
- 在全球范围内发现的R717L替代物影响基质通道运输.
- 替代Q176K增强了抗生素结合和排泄效率.
- 针对排泄仍然是打击抗生素耐药性的关键策略.
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