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孤儿应答调节因子RevSC21控制猪链球菌2型与人喉上皮细胞的黏附及毒力基因的表达。

The orphan response regulator RevSC21 controls the attachment of Streptococcus suis serotype-2 to human laryngeal epithelial cells and the expression of virulence genes.

作者信息

Wu Tao, Chang Haitao, Tan Chen, Bei Weicheng, Chen Huanchun

机构信息

Division of Animal Pathogens, State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.

出版信息

FEMS Microbiol Lett. 2009 Mar;292(2):170-81. doi: 10.1111/j.1574-6968.2008.01486.x. Epub 2009 Feb 5.

DOI:10.1111/j.1574-6968.2008.01486.x
PMID:19210676
Abstract

Streptococcus suis-2 is an important zoonotic pathogen that causes serious diseases such as meningitis, septicemia, endocarditis, arthritis and septic shock in pigs and humans. Little is known about the regulation of virulence gene expression in S. suis-2. In the present study, we characterized an orphan transcriptional regulator, designated RevSC21. The RevSC21 gene was cloned and the sequence was determined. Deletion of the revSC21 gene of S. suis-2 yielded a mutant strain, SC211, which exhibited a significant decrease in adherence to cell line Hep-2, and lacked hemolytic activity. Quantification of expression levels of known S. suis-2 SC21 virulence genes by real-time PCR in vitro and in vivo revealed that RevSC21 influences the expression of mrp, ef, sly, fbps, sod, rpob, gyra hyl, cps and gapdh virulence-associated genes. SC211 was shown to be attenuated in a 50% lethal dose assay and bacteriology, indicating that RevSC21 plays an important part in the pathogenesis of S. suis-2 infection. Mutant SC211 was 100% defective in virulence in CD1 mice at up to 10(7) CFU, and provided 100% protection when challenged with 10(7) CFU of the SC21 strain.

摘要

猪链球菌2型是一种重要的人畜共患病病原体,可在猪和人类中引起严重疾病,如脑膜炎、败血症、心内膜炎、关节炎和感染性休克。目前对猪链球菌2型毒力基因表达的调控知之甚少。在本研究中,我们鉴定了一个孤儿转录调节因子,命名为RevSC21。克隆了RevSC21基因并测定了其序列。缺失猪链球菌2型的revSC21基因产生了一个突变株SC211,该突变株对Hep-2细胞系的黏附能力显著降低,并且缺乏溶血活性。通过体外和体内实时PCR对已知的猪链球菌2型SC21毒力基因表达水平进行定量分析,结果显示RevSC21影响mrp、ef、sly、fbps、sod、rpob、gyra、hyl、cps和gapdh等毒力相关基因的表达。在50%致死剂量试验和细菌学实验中,SC211表现出毒力减弱,这表明RevSC21在猪链球菌2型感染的发病机制中起重要作用。突变株SC211在CD1小鼠中,当接种量高达10⁷CFU时,毒力完全丧失,并且当用10⁷CFU的SC21菌株攻击时,能提供100%的保护。

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