细菌病原体提供水/溶液透通道作为一种毒性策略
Kinya Nomura1,2, Felipe Andreazza1, Jie Cheng3
1Department of Biology, Duke University, Durham, NC 27708, USA.
bioRxiv : the preprint server for biology
|August 7, 2023
概括
AvrE/DspE家族的细菌效应体形成类似毛细菌的通道,使病原体具有毒性. 聚胺胺树状体抑制这些通道,提供一种潜在的策略来对抗植物和动物的感染.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 细菌的III型分泌系统向宿主细胞输送效应蛋白,这对病变发生至关重要.
- AvrE/DspE家族的作用因子是植物病原体细菌中保存的毒性因子,诱导诸如浸水和细胞死亡等症状.
- 几十年来,AvrE/DspE效应器的精确生化功能一直是难以捉摸的.
研究的目的:
- 阐明AvrE/DspE家族效应物的生化功能和结构.
- 为了确定AvrE/DspE效应器功能的潜在抑制剂.
主要方法:
- 结构分析揭示了AvrE/DspE效应器的β-桶孔状折叠.
- 在Xenopus卵细胞中进行功能性测试,以评估离子和水的透性.
- 脂质体复制以确认通道活动.
- 使用聚胺胺 (PAMAM) 树状体对孔阻塞物的化学选.
主要成果:
- AvrE/DspE效应器形成β-桶通道,类似于细菌毛孔.
- 这些通道促进了进出流,水的透性和依赖于度的细胞胀.
- 在脂质体中证实了DSPE通道活性,允许小分子通过.
- 在体外和体内,PAMAM树状体有效地抑制了DSPE/AvrE通道及其毒性活动.
结论:
- AvrE/DspE 效应器作为跨包膜蛋白通道,解释了它们在细菌病原性中的作用.
- PAMAM树枝状体代表了一类有前途的抑制剂,其向这些必不可少的毒性因素.
- 这一发现为细菌病原和潜在的治疗策略提供了重要的概念和实践见解.
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