抗甲素黄金葡萄球菌改变细胞壁糖化以逃避免疫力
David Gerlach1,2, Yinglan Guo3, Cristina De Castro4
1Interfaculty Institute of Microbiology and Infection Medicine, Infection Biology, University of Tübingen, Tübingen, Germany.
Nature
|November 23, 2018
概括
通过改变其表面聚合物 - - 壁状铁酸 (WTA) - - 来逃避免疫反应. 一种新的酶TarP修改了WTA,减少了抗体识别,并阻碍了针对MRSA感染的疫苗开发.
科学领域:
- 微生物学和免疫学
- 疫苗开发
- 结构生物学
背景情况:
- 甲素耐药黄金葡萄球菌 (MRSA) 导致严重的,往往致命的人类感染.
- 现有的MRSA疫苗没有成功,部分原因是抗体反应变化.
- 墙体铁酸 (WTA) 是人类抗体的主要表面抗原.
研究的目的:
- 调查WTA糖化变化是否有助于MRSA免疫规避.
- 了解TarP介导的WTA修饰的机制及其对免疫识别的影响.
- 探索TarP作为新型MRSA治疗的潜在目标.
主要方法:
- 对MRSA克隆进行分析,以检测其它WTA糖基转移酶的存在.
- TarP酶活性及其对WTA结构的影响的生物化学特征.
- 测量对TarP修饰的WTA的抗体反应的免疫学测定.
- 与WTA组件和UDP-GlcNAc组合的TarP的结构分析
主要成果:
- MRSA克隆CC5和CC398具有编码TarP的prophages,这是一个替代的WTA糖基转移酶.
- 与TarS不同,TarP对WTA进行了不同的修饰,导致抗体 (IgG) 识别显著降低.
- 修改为TarP的WTA未能保护小鼠免受MRSA感染,这凸显了它在免疫逃避中的作用.
- 结构研究阐明了TarP改变WTA的糖化机制.
结论:
- 作为一种免疫规避策略,MRSA采用了TarP介导的WTA修饰.
- 这种机制降低了关键表面抗原的免疫性,导致治疗挑战.
- TarP是S. aureus逃避宿主防御的能力的一个关键因素,也是治疗干预的潜在目标.
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