作为MHC/HLA-I受体的新兴肠球菌孔形成毒素
Xiaozhe Xiong1, Songhai Tian1, Pan Yang2
1Department of Urology, Boston Children's Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
Cell
|March 8, 2022
概括
研究人员发现Enterococcus形成毛孔的毒素 (Epxs) 导致多种抗药性感染. 这些毒素向人类白细胞抗原I类 (HLA-I) 复合体,突出了Enterococcus的新毒性机制.
科学领域:
- 微生物学
- 免疫学
- 结构生物学
背景情况:
- 肠球菌是开始性细菌,也是多药性感染的重要来源.
- 形成毛孔的毒素 (PFT) 是许多细菌病原体的关键毒性因素.
研究的目的:
- 识别和描述Enterococcus物种中的新型毛孔形成毒素.
- 阐明Enterococcus介导的致病和宿主细胞相互作用的分子机制.
主要方法:
- 用全基因组的CRISPR-Cas9选来识别毒素受体.
- 确定毒素结构的结构生物学技术.
- 基于细胞的测定和器官模型来评估毒素诱导的细胞毒性.
- 在体外共同培养实验以评估细菌毒性.
主要成果:
- 在E. faecalis,E. faecium和E. hirae的全球菌株中发现了一种新的Enterococcus孔隙形成毒素 (Epxs).
- Epx毒素具有独特的β-桶结构,具有明显的顶部域.
- 人类白细胞抗原I类 (HLA-I) 被确定为Epx2和Epx3的受体,具有与人类和某些动物MHC-I分子的优先结合,但不是小鼠.
- 干扰素治疗增强了细胞对Epx2和Epx3的敏感性.
- 产生Epx2的Enterococcus faecium通过破坏人类外周血液单核细胞和肠道器官来证明毒性,毒性被Epx2抗体中和.
结论:
- 菌孔形成毒素 (Epxs) 是一种新发现的细菌毒性因子.
- Epx毒素与HLA-I复合体的相互作用为Enterococcus提供了一个逃避宿主免疫力并引起疾病的机制.
- 针对Epx毒素提供了针对多抗药性Enterococcus感染的潜在治疗策略.
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