免疫蛋白质对Ntox15核酶效应因子域的结构性破坏可以防止Bacteroidales的VI型分泌系统中毒
Dustin E Bosch1, Romina Abbasian1, Bishal Parajuli1
1Department of Pathology, Carver College of Medicine, University of Iowa , Iowa City, Iowa, USA.
mBio
|June 22, 2023
概括
细菌使用VI型分泌系统 (T6SS) 进行竞争. 一种新的核酶效应因子 (Tde1) 和其免疫蛋白 (Tdi1) 显示出一种独特的细菌防御机制,可能在炎症性肠病中发挥作用.
科学领域:
- 微生物学 微生物学
- 结构生物学 结构生物学
- 人类健康 人类健康 人类健康
背景情况:
- 细菌是主要的结肠居民,与炎症性肠病 (IBD) 有关.
- 第六类分泌系统 (T6SS) 对于细菌的竞争和殖民至关重要.
- 核酶效应体 (Tde) 和它们的相关免疫蛋白 (Tdi) 是细菌防御系统的一部分.
研究的目的:
- 为了识别和描述一个新的水平转移T6SS在Bacteroidales.
- 阐明由Tde核酶及其免疫蛋白调解的细菌间对抗的机制.
- 研究Tde-T6SS系统在炎症性肠病中的潜在作用.
主要方法:
- 在 Bacteroidales 中识别水平转移的 T6SS 和 Tde 效应器.
- 表达和特征的Tde效应因子和Tdi免疫蛋白.
- 使用Tde/Tdi复合物的晶体学进行结构分析.
- 在IBD患者元基因组中对Tde和T6SS基因丰富的生物信息分析.
主要成果:
- 鉴定了一种具有Ntox15家族核酶效应因子 (Tde1) 的新型T6SS,它调解了细菌间的对抗性.
- 免疫蛋白 (Tdi1) 通过诱导破坏效应物的活性部位的形状变化来保护Tde1的攻击.
- 结构研究揭示了一个保存的机制,Tdi插入Tde核心,分裂核酶折叠.
- 在性结肠炎患者的甲基因组中,Tde和T6SS基因被丰富.
- 这种Tde/Tdi相互作用机制与其他已知的多态毒素免疫系统不同.
结论:
- 在 Bacteroidales 中水平转移的 Tde 编码 T6SS 中介于竞争性增长,并可能导致IBD.
- 独特的Tdi介导免疫机制提供了对Tde效应者的广泛保护.
- 这些发现突出了一个新的细菌防御系统,对肠道微生物组动态和炎症性疾病有影响.
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