综合调节的马-血解素表达影响金黄色葡萄球菌 毒性 毒性
Mariane Pivard1, Isabelle Caldelari2, Virginie Brun3,4
1CIRI, Centre International de Recherche en Infectiologie, Université de Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS UMR5308, ENS de Lyon, Lyon, France.
Microbiology spectrum
|June 22, 2023
概括
黄金葡萄球菌 (Staphylococcus aureus) gamma-hemolysin CB (HlgCB) 毒素水平因遗传变化而在肺炎分离物中显著变化. 一个单个5' UTR SNP极大地影响HlgC转换,影响病毒性.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 病变的发生和发病.
背景情况:
- 黄金葡萄球菌产生孔形成毒素,如马-血解素CB (HlgCB),准C5a受体.
- HlgCB类似于Panton-Valentine leucocidin (PVL),有助于社区获得性肺炎 (CAP) 的严重程度.
- 在临床分离物中存在HlgCB表达的变化,影响S. aureus的毒性.
研究的目的:
- 研究S. aureus临床菌株中HlgCB表达和蛋白质生产变化的分子基础.
- 确定遗传变异对HlgCB水平和HlgC/HlgB比率的影响.
- 在肺炎模型中,将HlgCB水平与S. aureus毒性相关联.
主要方法:
- 在39个CAP隔离物中使用质谱测量对HlgCB的绝对量化.
- 在促进剂,mRNA处理和翻译水平上分析hlgCB表达.
- 在hlgCB的监管区域中识别单核酸多态 (SNP).
- 在子肺炎模型中评估HlgCB毒性.
主要成果:
- 在分离物之间观察到HlgC和HlgB产量的显著变化,在10%的菌株中观察到分离水平.
- HlgCB水平和HlgC/HlgB比率取决于hlgC促进体活性,mRNA处理和翻译.
- 在hlgCB mRNA的5' UTR中的单个SNP在USA300菌株中严重损害了HlgC翻译.
- 在子肺炎模型中,高HlgCB水平与死亡率相关.
结论:
- 微妙的基因组变异,特别是非编码区域的SNP,可以显著影响S. aureus HlgCB表达和毒性.
- 在PVL阴性肺炎菌株中,HlgCB在S. aureus毒性中起着至关重要的作用.
- 了解这些调节机制是破译细菌病原体和开发向疗法的关键.
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