Nur77保护膀泌尿层免受细胞内细菌感染
Christina A Collins1, Chevaughn Waller2, Ekaterina Batourina2
1Department of Pediatrics, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA.
Nature communications
|September 27, 2024
概括
核受体Nur77可以防止由大肠杆菌引起的尿路感染. 激活Nur77可能为持久性细菌感染提供一种新的抗生素节约疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 分子生物学分子生物学
背景情况:
- 细胞内格拉姆阴性细菌感染构成了全球卫生挑战.
- 众所周知,核受体Nur77 (NR4A1) 可以检测细菌脂聚糖 (LPS).
- Nur77在控制细胞内细菌感染中的作用仍然未被探索.
研究的目的:
- 研究Nur77在防御细胞内细菌感染,特别是尿病原性大肠杆菌 (UPEC) 的作用.
- 探索Nur77激动剂治疗尿路感染 (UTI) 的治疗潜力.
主要方法:
- 利用UPEC感染的小鼠模型来评估Nur77缺乏对膀感染的影响.
- 在实验室中检查了小分子Nur77激动剂cytosporone B对人类尿细胞中UPEC入侵和驱逐的作用.
- 量化UPEC细胞内细菌群落 (IBCs) 和膀感染水平在小鼠中治疗了B.cytosporone.
主要成果:
- 在小鼠中,Nur77缺乏导致UPEC IBC形成的增加和持续的膀感染.
- 细胞素B治疗抑制了UPEC的入侵,并促进了细菌从人类尿细胞中排出.
- 药理上激活Nur77显著降低了UPEC IBC形成和膀感染在体内.
结论:
- Nur77对细胞内UPEC膀感染起着关键的保护作用.
- 针对Nur77使用诸如cytosporone B之类的激动剂显示出作为治疗尿路感染的抗生素节约策略的希望.
- 这项研究确定了一种新的治疗途径,用于管理持久性细菌感染.
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