在Campylobacter中,强大的多药物排泄RE-CmeABC的基于突变的机制和演变
Lei Dai1, Zuowei Wu1, Orhan Sahin2
1Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011.
概括
在Campylobacter jejuni中,CmeABC排泄的一种新变体RE-CmeABC,由于RE-CmeB及其促进体的突变,增强了抗生素耐药性. 这种变种正在全球传播,具有临床相关性.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 进化生物学 进化生物学
背景情况:
- 抵抗-结节-细胞分裂 (RND) 超级家族介导了格拉姆阴性病原体的抗生素耐药性.
- 坎比洛巴克特 (Campylobacter jejuni) 使用RND转运器CmeABC进行抗生素挤出.
- 一种强效的变种RE-CmeABC在临床隔离物中增强了多药耐药性.
研究的目的:
- 阐明RE-CmeABC功能增益背后的分子机制.
- 调查RE-CmeABC的进化轨迹和全球传播.
主要方法:
- 在RE-CmeB,RE-CmeA和RE-CmeC中对氨基酸替代物的分析.
- 核酸突变的识别在流动操作的促进器区域.
- 全球监测和RE-cmeABC分布在坎比洛巴克特菌株的进化分析.
主要成果:
- 在RE-CmeB中的氨基酸替代和促进子突变驱动RE-CmeABC的增强功能.
- 在全球范围内,RE-cmeABC分布在多种C. jejuni菌株中,这表明水平基因转移.
- 携带RE-cmeABC的分离物与人类感染和疫情有关,突出显示了临床意义.
结论:
- 一个基于突变的机制是RE-CmeABC功能增益的基础,主要涉及RE-CmeB.
- 揭示了RE-CmeB在大肠杆菌的起源和在C. jejuni的扩张,可能是由抗生素压力驱动的.
- RE-CmeB正在接受选择性扫描,这表明它在Campylobacter抗生素耐药性适应中的关键作用.
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