内膜蛋白YhiM连接铜和CpxAR外应激反应在尿病原性E. 大肠杆菌
Panatda Saenkham-Huntsinger1, Matthew Ritter1, George L Donati2
1Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA.
mBio
|March 12, 2024
概括
一个缺乏膜蛋白YhiM的UPEC突变体,显示出铜抗性增加. 这项研究揭示了YhiM在感染期间的UPEC生存中与铜恒温和外应激反应的联系.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 细菌病原体的产生
背景情况:
- 泌尿病原性大肠杆菌 (UPEC) 导致尿路感染 (UTI).
- 铜 (Cu) 在天生的免疫力中起作用,但对细菌可能有毒.
- 细菌的铜恒温对于生存至关重要,特别是在感染期间.
研究的目的:
- 在UPEC中识别参与铜进口和恒温的基因.
- 研究假设的内膜蛋白YhiM在抗铜性中的作用.
- 阐明铜应力与细菌包膜应力反应之间的联系.
主要方法:
- 在UPEC CFT073.3.中使用转子子 (Tn5) 插入突变体进行前向遗传查.
- 铜耐药突变的特征,包括那些缺乏yhiM的突变.
- 对细胞铜含量,基因表达 (copA,cpxP) 和调节通路 (CueR,CpxR,NlpE) 的分析.
- 在尿路感染的小鼠模型中评估UPEC适应性.
主要成果:
- 一个先进的基因选发现了32种独特的抗铜UPEC突变.
- 缺少yhiM的突变者表现出明显增加的抗铜性.
- 失去了YhiM减少了细胞中的铜含量,并增加了铜排泄copA的表达.
- 在ΔyhiM突变体中,CpxAR外应力反应系统被激活,这对于铜抗性至关重要.
- 在ΔyhiM突变体中的CpxAR激活独立于NlpE.
- 在小鼠UTI模型中,YhiM对于优化UPEC健身至关重要.
结论:
- 在UPEC中,YhiM是铜恒温的关键调解者.
- YhiM将细菌适应铜应力与CpxAR依赖的外应力反应联系在一起.
- 在UPEC中,在铜应力过程中,CpxAR系统以NlpE独立的方式被激活.
- 在尿路感染期间,YhiM对于UPEC的生存和健康至关重要.
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