鞭毛切换反转的重复影响鞭毛基因表达的异质性,从而导致C. difficile RT027/MLST1的毒性
Nguyen T Q Nhu1, Huaiying Lin2, Ying Pigli3
1Department of Medicine, University of Chicago, Chicago, IL 60637, USA; Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA.
Cell reports
|June 12, 2025
概括
艰难的Clostridioides RT027菌株显示出不同的感染严重程度. 在这些C. difficile菌株中,较大的鞭状基因表达异质性与增加的毒性和疾病严重程度有关.
科学领域:
- 微生物学 微生物学
- 传染性疾病 传染性疾病
- 遗传学 是一个遗传学.
背景情况:
- 艰难菌 (C. difficile) RT027菌株导致各种感染,从轻微到危及生命.
- 在C. difficile感染严重程度的这种变化背后的分子机制仍然不清楚.
研究的目的:
- 调查C. difficile RT027临床分离物中鞭毛基因表达异质性和毒性之间的关系.
- 阐明C. difficile中可变的鞭毛基因表达的遗传基础.
主要方法:
- 对C. difficileRT027临床分离物的比较分析.
- 对鞭状基因表达模式的检查.
- 反向重复 (IR) 序列长度,基因表达异质性和体内病毒性之间的相关性分析.
主要成果:
- 具有较大的鞭毛基因表达异质性的分离物体在体内表现出更高的毒性.
- C. difficile鞭毛基因的相变表达通过flgB 5' UTR的特定位点逆转来控制.
- 交换区中较长的IR序列,特别是6A/6T IR,与较短的IR (>99% ON或OFF) 相比,与更大的表型异质性 (60%-75% ON) 和更严重的疾病结局有关.
结论:
- 鞭毛基因表达的现型异质性是导致C. difficile感染严重程度变化的潜在因素.
- 鞭毛切换区域内IR序列的长度会影响基因表达异质性和C. difficile的毒性.
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