猪链球菌2型硫氧还蛋白还原酶介导细菌应激与致病作用

Thioredoxin reductase contributes to stress response and pathogenicity of Streptococcus suis type 2

摘要:

【背景】硫氧还蛋白还原酶（thioredoxin reductase，TRR）是硫氧还蛋白系统关键组成部分，对病原菌应对体内外氧化应激、调节细菌稳态和介导致病过程具有重要作用。【目的】探究硫氧还蛋白还原酶TRR在人畜共患猪链球菌2型感染过程中参与的生物学效应。【方法】同源重组法构建猪链球菌2型硫氧还蛋白还原酶trr基因缺失株（Δtrr）及回补株（cΔtrr），通过细菌染色、点板计数、体外细胞和动物感染模型等试验比较分析trr基因对细菌形态、抗应激反应及致病过程的影响。【结果】缺失trr对猪链球菌2型形态与生长特性的影响不大，但可增强细菌抗热应激、氧化应激和酸应激能力，缺失株对上皮细胞黏附力下降，侵袭进入脑血管内皮细胞作用显著降低，易于被吞噬细胞吞噬清除，对小鼠模型致病效应显著减弱。【结论】猪链球菌2型TRR因子参与细菌应激反应，介导细菌黏附、侵袭等致病过程，是猪链球菌2型新的潜在毒力因子。

Abstract:

[Background] The thioredoxin reductase (TRR), one of the key components in the thioredoxin system, plays a key role in the oxidative stress response, homeostasis, and infection of pathogens.[Objective] To examine the role of TRR in the infection of Streptococcus suis type 2 (SS2), a zoonotic pathogen. [Methods] The trr-deleted mutant (Δtrr) and complementation strain (cΔtrr) of SS2 were constructed by homologous recombination on the basis of the wild-type (WT) strain HA9801. The Gram staining, plate counting, and cell and mouse infection assays were employed to examine the morphological characteristics, stress resistance, and infection process of the strains. [Results] The deletion of trr showed no effect on the morphological or growth characteristics of SS2, while it enhanced the tolerance to heat, oxidative, and acid stress conditions compared with WT. Δtrr presented reduced adhesion on murine epithelial cells and invasion capacity in cerebrovascular endothelial cells. It was easily to be phagocytosed and presented lower pathogenicity in RAW264.7 cells and mice. [Conclusion] TRR is involved in the stress responses, adhesion, and invasion and serves as a novel virulence factor for SS2.