肠出血性大肠杆菌利用宿主和微生物群衍生的L-酸盐作为肠道殖民的信号分子
Bin Liu1,2, Lingyan Jiang1,2, Yutao Liu1,2
1TEDA Institute of Biological Sciences and Biotechnology, Nankai University, TEDA, Tianjin, 300457, P. R. China.
Nature communications
|November 9, 2023
概括
肠出血性大肠杆菌 (EHEC) O157:H7使用L-酸盐获得能量并激活毒性基因,促进肠道殖民. 针对DcuS/DcuR系统可能为EHEC感染提供新的治疗方法.
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:
- 哺乳动物的肠道拥有复杂的微生物群落,需要病原体争夺资源并适应宿主环境.
- 细菌病原体必须调节基因表达以在胃肠道内进行殖民和毒性.
研究的目的:
- 调查L-酸盐代谢和信号传递在肠道出血性大肠杆菌 (EHEC) O157:H7肠道殖民中的作用.
- 阐明L-酸盐影响EHEC病毒性基因表达和殖民化的分子机制.
主要方法:
- 在EHEC O157:H7.7.中利用基因操纵 (基因删除) 来研究DcuABC传送器和DcuS/DcuR两组系统的功能.
- 研究了L-酸盐的进口,转化为烟酸盐,以及其在无氧呼吸和毒性基因激活中的作用.
- 评估了破坏L-酸盐传感途径对婴儿子模型中EHEC殖民化的影响.
主要成果:
- EHEC O157:H7通过DcuABC运输体进口和代谢L-酸盐,产生用于无氧呼吸的烟酸盐并促进肠道殖民.
- L-酸盐作为一个信号分子,激活DcuS/DcuR两个组成系统.
- DcuS/DcuR系统调节主毒性调节器Ler,这反过来又激活了对上皮细胞粘附至关重要的肠细胞消灭 (LEE) 基因的位点.
- 删除dcuS或dcuR显著损害了EHEC O157:H7在体内的殖民.
结论:
- L-酸盐是EHEC O157:H7的关键营养物质和信号分子,对于毒性和肠道殖民是必不可少的.
- DcuS/DcuR-Ler路径代表了控制EHEC病原性的关键监管机制.
- 针对这些基因或操纵肠道生理学呈现了潜在的治疗策略来对抗EHEC感染.
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