酸控制依赖的退出和发展在Toxoplasma gondii中
Kisaburo Nagamune1, Leslie M Hicks, Blima Fux
1Department of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA.
Nature
|January 11, 2008
概括
植物激素酸 (ABA) 调节寄生虫Toxoplasma gondii中的信号,控制诸如宿主细胞退出等关键事件. 这一发现为毒素菌提供了潜在的治疗点.
科学领域:
- 寄生虫学的寄生虫学
- 分子生物学分子生物学
- 信号传递 信号传递
背景情况:
- 信号传递对复合体寄生虫的功能至关重要,如运动性和外出.
- 与其他真核生物相比,寄生虫中信号传递的分子机制在很大程度上是未知的.
- 像*Toxoplasma gondii*这样的阿皮复合体寄生虫是人类显著的病原体.
研究的目的:
- 为了研究植物激素酸 (ABA) 在控制*Toxoplasma gondii*中的信号传递中的作用.
- 为了阐明ABA诱导的释放的分子基础及其对寄生虫的下游影响.
- 为了探索针对*Toxoplasma gondii*中的ABA合成的治疗潜力.
主要方法:
- 用外源性ABA治疗*Toxoplasma gondii*的方法.
- 循环ADP核糖酶 (cADPR) 产量的量化.
- 测量依赖的蛋白质分泌和寄生虫的外出.
- 使用HPLC和GC-MS确认内源性ABA生产.
- 用弗路里抑制ABA合成.
- 感染小鼠模型以评估治疗疗效.
主要成果:
- 外源ABA诱导了cADPR的形成,刺激了依赖的分泌,并促进了寄生虫的退出.
- 在 *Toxoplasma gondii* 中确认了内源性 ABA 生产.
- 抑制ABA合成延迟了出血并促进了休眠囊的形成.
- 通过ABA介导的信号决定了溶性和慢性寄生虫发育之间的切换.
- 一种特定的ABA合成抑制剂在小鼠模型中阻止了毒素菌.
结论:
- 酸 (ABA) 是 *Toxoplasma gondii* 中信号传递和发育过渡的关键调节者.
- 可能从藻类内生生体获得的ABA合成途径代表了潜在的治疗标.
- 向ABA合成提供了一个有前途的策略来治疗毒素菌.
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