马链球菌动物园流行亚种的内源性 I-C 型 CRISPR-Cas 系统促进生物膜形成和致病性

Honglin Xie, Riteng Zhang, Ziyuan Li, Ruhai Guo, Junda Li, Qiang Fu, Xinglong Wang, Yefei Zhou
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引用次数: 0

摘要

马链球菌动物流行亚种(SEZ)是一种重要的人畜共患病原体,可导致家畜败血症、脑膜炎和乳腺炎。最近有报道称,美国爆发的猪瘟死亡率很高。传统上,CRISPR-Cas 系统被认为具有适应性免疫功能,但它也与基因调控、细菌病理生理学、毒力和进化有关。SEZ 分离物中普遍存在的 I-C 型 CRISPR-Cas 系统似乎在调节 SEZ 的致病性方面发挥着关键作用。通过构建Cas3突变株(ΔCas3)和CRISPR缺陷株(ΔCRISPR),我们证明该系统能显著促进生物膜的形成和细胞粘附。然而,CRISPR-Cas 系统的缺陷并不影响细菌的形态或胶囊的产生。体外研究表明,CRISPR-Cas 系统增强了 RAW264.7 细胞的促炎反应。ΔCas3和ΔCRISPR突变株在小鼠中的死亡率降低,同时特定器官中的细菌量也减少了。RNA-seq分析揭示了两种突变株的不同表达模式,其中ΔCas3显示了更广泛的差异表达基因,占ΔCRISPR中观察到的差异基因的70%以上。这些基因主要与脂质代谢、ABC 转运系统、信号转导和法定人数感应有关。这些发现加深了我们对CRISPR-Cas系统在SEZ致病过程中复杂作用的理解,并为开发抗感染的创新治疗策略提供了宝贵的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Endogenous Type I-C CRISPR-Cas system of Streptococcus equi subsp. zooepidemicus promotes biofilm formation and pathogenicity
Streptococcus equi subsp. zooepidemicus (SEZ) is a significant zoonotic pathogen that causes septicemia, meningitis, and mastitis in domestic animals. Recent reports have highlighted high-mortality outbreaks among swine in the United States. Traditionally recognized for its adaptive immune functions, the CRISPR-Cas system has also been implicated in gene regulation, bacterial pathophysiology, virulence, and evolution. The Type I-C CRISPR-Cas system, which is prevalent in SEZ isolates, appears to play a pivotal role in regulating the pathogenicity of SEZ. By constructing a Cas3 mutant strain (ΔCas3) and a CRISPR-deficient strain (ΔCRISPR), we demonstrated that this system significantly promotes biofilm formation and cell adhesion. However, the deficiency in the CRISPR-Cas system did not affect bacterial morphology or capsule production. In vitro studies showed that the CRISPR-Cas system enhances pro-inflammatory responses in RAW264.7 cells. The ΔCas3 and ΔCRISPR mutant strains exhibited reduced mortality rates in mice, accompanied by a decreased bacterial load in specific organs. RNA-seq analysis revealed distinct expression patterns in both mutant strains, with ΔCas3 displaying a broader range of differentially expressed genes, which accounted for over 70% of the differential genes observed in ΔCRISPR. These genes were predominantly linked to lipid metabolism, the ABC transport system, signal transduction, and quorum sensing. These findings enhance our understanding of the complex role of the CRISPR-Cas system in SEZ pathogenesis and provide valuable insights for developing innovative therapeutic strategies to combat infections.
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