一种细菌毒性蛋白通过抑制细菌自身的F1Fo ATP合成酶来促进病原性
Eun-Jin Lee1, Mauricio H Pontes, Eduardo A Groisman
1Department of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale School of Medicine, 295 Congress Avenue, New Haven, CT 06536-0812, USA.
Cell
|July 6, 2013
概括
毒性蛋白MgtC有助于像沙门氏菌这样的病原体通过破坏它们的能量生产,在宿主细胞内生存. MgtC干扰F1Fo ATP合成酶,影响细菌ATP水平和病原性.
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:
- 细胞内病原体沙门氏菌 (Salmonella enterica) 和结核菌 (Mycobacterium tuberculosis) 依赖MgtC病毒性蛋白质在巨细胞内生存.
- 在小鼠模型中,MgtC对于引起致命感染至关重要.
- 与针对宿主机械的分泌因子不同,MgtC在细菌成分上以细胞内作用.
研究的目的:
- 阐明MgtC对病原体毒性有所贡献的分子机制.
- 为了研究MgtC与沙门氏菌产生能量的F1Fo ATP合成酶的相互作用.
- 确定MgtC在调节细胞内ATP水平和致病性的作用.
主要方法:
- 生物化学试验研究MgtC与F1Fo ATP合成酶之间的相互作用.
- 对细菌囊泡中的质子转位和ATP合成的分析.
- 构建和表征mgtC无突变和MgtC变体.
- 评估细菌ATP水平,细胞质pH值和体内致病性.
主要成果:
- MgtC直接与F1Fo ATP合成酶的"a"子单元相互作用.
- 这种相互作用抑制了ATP驱动的质子转位和NADH驱动的ATP合成.
- mgtC无突变体表现出高ATP水平和酸性细胞质.
- 过度表达MgtC导致ATP水平降低.
- 阻止F1FoATP合成酶结合的特定MgtC突变取消了ATP水平的控制,并降低了病原性.
结论:
- MgtC是一种独特的毒性因子,通过抑制细菌F1Fo ATP合成酶来增强病原性.
- 这种机制允许病原体操纵其细胞内环境和能量代谢以求生存.
- 与F1Fo ATP合成酶的干扰代表了MgtC使用的一种新的毒性策略.
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