在Clostridioides difficile中,基因酶介导的基因素耐药性操作子的交叉调节
1Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA.
Molecular microbiology
|May 1, 2024
概括
克洛斯特里迪奥伊德困难的vanG操作调节涉及出乎意料的histidine激酶 (HKs) 超出VanS. 这些HKs,CD35990和CD22880,可以激活VanR响应万科米辛和拉莫普拉宁,影响抗生素耐药性.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 抗生素耐药性 抗生素耐药性
背景情况:
- 双酸D-Ala-D-Ala对丁糖甘的合成至关重要,也是万科胺的标.
- 困难菌 Clostridioides 利用 vanG 操作子合成 D-Ala-D-Ser,取代 D-Ala-D-Ala,并可能产生对万科素的抗药性.
- 范G操作子通常由VanRS双组件系统调节,但表现出不够的诱导由菌素对抗性.
研究的目的:
- 为了研究在没有VanS基因酶 (HK) 的情况下,万科米辛和拉莫普拉宁对vanG操作子的意外诱导.
- 为了确定替代的HK,负责VanG操作的VanR依赖性调节.
- 了解非亲属HKs的VanR激活的交叉调节机制.
主要方法:
- 在Clostridioides difficile.中对vanG操作子调节的遗传分析.
- 鉴定涉及抗生素反应的新型歇斯蒂丁激酶 (CD35990,CD22880).
- RNA测序 (RNA-Seq) 用于识别CD35990和CD22880.0的候选标.
主要成果:
- 范G操作子是诱导的vancomycin和拉莫普拉宁在一个VanR-依赖的方式,即使没有VanS HK.
- CD35990和CD22880被确定为参与该交叉监管的替代HK.
- 在CD35990或CD22880的突变没有影响野生类型细胞中vanG运调节,这表明VanS通常会阻止交叉激活.
- 在没有已知的HK的情况下,VanR的过度生产导致了高vanG操作子表达,表明VanR激活的替代酸盐供体.
结论:
- 替代性歇斯蒂丁激酶 (CD35990,CD22880) 在调节Clostridioides difficile中的vanG操作子方面发挥作用.
- VanS通常会抑制VanR被非同类HKs交叉激活.
- 范R激活不仅仅依赖于范S,这表明更广泛的调节网络影响了C. difficile的抗生素耐药性.
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