在Streptococcus agalactiae中的辅助分泌系统调节蛋白质分泌,抗压力,粘附,免疫逃避和毒性
Jizhen Cao1, Han Li1, Qing Han1
1State Key Laboratory of Biocontrol/Guangdong Provincial Key Laboratory of Improved Variety Reproduction in Aquatic Economic Animals and Institute of Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, Guangdong, PR China.
Fish & shellfish immunology
|February 5, 2025
概括
辅助分泌系统对于Streptococcus agalactiae的生存和毒性至关重要. 删除它会降低细菌的应激耐受性,粘附性和鱼类死亡率,为活体减弱疫苗提供了潜力.
科学领域:
- 微生物学 微生物学
- 细菌病原体的产生
- 鱼类免疫学 鱼类免疫学
背景情况:
- 杆菌 (Streptococcus agalactiae) 是人类和鱼类的重要病原体.
- 细菌分泌系统调节宿主-病原体相互作用.
- 辅助分泌系统在S. agalactiae毒性的作用在很大程度上是未知的.
研究的目的:
- 研究S. agalactiae的辅助分泌系统的基本性和功能.
- 确定辅助分泌系统删除对细菌活力,包膜稳定性和宿主-病原体相互作用的影响.
- 在鱼类模型中评估S. agalactiae辅助分泌系统删除突变体 (ΔaccSec) 的毒性.
主要方法:
- 在S. agalactiae的辅助分泌系统中构建同源的基于重组的删除突变 (ΔaccSec).
- 对DaccSec突变体中的细菌活力,细胞死亡和细胞外蛋白质分泌的分析.
- 评估应激耐受性,包膜稳定性,对宿主细胞的粘附性,以及对先天免疫机制 (全血,细胞) 的抵抗性.
- 在腹腔内注射后对鱼 (Oreochromis niloticus) 的致病性和殖民性的评估.
- 测量宿主免疫反应,包括巨细胞的活性氧物种 (ROS) 和脏MHC-II和TLR-2转录水平.
主要成果:
- 辅助分泌系统对于S. agalactiae的生存能力至关重要;它的缺失导致了细胞死亡和溶解的增加.
- 突变的DaccSec显示出33种蛋白质的分泌量减少,压力耐受性降低,包膜稳定性受损.
- 致病性测定显示,对 ΔaccSec 突变的粘附性显著降低,对宿主免疫杀伤的抵抗性较低,鱼死亡率降低 (55.3-74.2%).
- 突变的DaccSec表现出减少了鱼的殖民化,并诱导了更高的ROS水平,并提高了宿主脏中MHC-II和TLR-2表达的调节.
结论:
- 附属分泌系统对于S. agalactiae的毒性至关重要,特别是在保持包裹完整性,促进粘附和逃避宿主免疫力方面.
- 删除辅助分泌系统减弱了S. agalactiae,导致鱼类的致病性降低.
- 这些发现为S. agalactiae的毒性机制提供了洞察力,并支持开发针对这种重要鱼类病原体的活体减弱疫苗.
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