HP0197 contributes to CPS synthesis and the virulence of Streptococcus suis via CcpA.

HP0197 contributes to CPS synthesis and the virulence of Streptococcus suis via CcpA.
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DOI:
10.1371/journal.pone.0050987
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Jin M
Jin M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhang A;Chen B;Yuan Z;Li R;Liu C;Zhou H;Chen H;Jin M

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猪链球菌2型(Streptococcussuisserotype2,SS2)是一种重要的猪源性疾病,是一种新型的人畜共患病,严重威胁着全球的公共卫生。细菌编码的未知功能的编码蛋白是研究致病机制的障碍。新的表面保护性抗原HP 0197是这些蛋白质中的一种,其与任何已知蛋白质都没有序列同源性。在本研究中,通过对小鼠和猪中的同基因突变体(Δ hp0197)的评价,确定该蛋白质参与细菌毒力。实验感染表明,Δ hp0197在感染过程中易于被清除,这可能是由于荚膜多糖(CPS)的厚度减小和吞噬阻力显著降低所致。基于微阵列的比较转录组分析表明,负责CPS合成的操纵子的抑制表达可能被CcpA活性逆转,CcpA活性通过CcpA和HPr-Ser-46-P与靶操纵子的分解产物响应元件(cre)的结合来控制碳分解产物的全局调节。该假设得到了以下事实的证实:通过电泳迁移率变动测定,与Δ hp0197相比,来自WT染色的纯化FLAG标记的HPr与CcpA表现出更高的与cre的结合活性,这表明磷酸化载体蛋白HPr在Δ hp0197中残基Ser-46(HPr-Ser-46 P)处的磷酸化水平较低。这表明HP 0197可以通过增强CcpA活性来调控糖利用和CPS合成相关基因的表达,从而增强S.猪。
Streptococcus suis serotype 2 (SS2), a major swine pathogen and an emerging zoonotic agent, has greatly challenged global public health. The encoding proteins with unknown functions the bacterium encodes are an obstruction to studies of the pathogenesis. A novel surface protective antigen HP0197 is one of these proteins which have no sequence homology to any known protein. In the present study, the protein was determined to be involved in bacterial virulence through an evaluation of the isogenic mutant (Δhp0197) in both mice and pigs. The experimental infection also indicated that Δhp0197 could be cleared easily during infection, which could be attributed to the reduced thickness of the capsular polysaccharides (CPS) and the significantly reduced phagocytotic resistance. Microarrays-based comparative transcriptome analysis suggested that the suppressed expression of the operon responsible for CPS synthesis might be reversed by CcpA activity, which controlled global regulation of carbon catabolite through the binding of the CcpA and HPr-Ser-46-P to the catabolite-responsive elements (cre) of the target operons. The hypothesis was approved by the fact that the purified FLAG-tagged HPr from WT stain exhibited a higher binding activity to cre with CcpA compared to the Δhp0197 by the Electrophoretic Mobility Shift Assay, suggesting lower level of phosphorylation of the phosphocarrier protein HPr at residue Ser-46 (HPr-Ser-46P) in Δhp0197. These indicated that HP0197 could enhance CcpA activity to control the expression of genes involved in carbohydrate utilization and CPS synthesis, thus contributing to the virulence of S. suis.
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