SPD_1495有助于肺炎链球菌中荚膜多糖的合成和毒性。,mSystems

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SPD_1495有助于肺炎链球菌中荚膜多糖的合成和毒性。
mSystems ( IF 5.0 ) Pub Date : 2020-02-25 , DOI: 10.1128/msystems.00025-20
Yun-Dan Zheng ₁ , Ying Pan ₁ , Ke He ₁ , Nan Li ₁ , Donghong Yang ₁ , Gao-Fei Du ₁ , Ruiguang Ge ₂ , Qing-Yu He ₃ , Xuesong Sun ₃

Affiliation

肺炎链球菌是一种革兰氏阳性人类病原体，可在人类中引起一系列严重疾病。在NCBI数据库中，肺炎链球菌的SPD_1495被注释为一种假想的ABC糖结合蛋白，但有关SPD_1495的详细生物学功能的报道很少。为了全面研究SPD_1495对肺炎链球菌细菌毒力的影响，我们构建了一个缺失突变体（D39Δspd1495）和一个过表达菌株（D39spd1495 +）。对野生型D39菌株（D39-WT）和D39Δspd1495的基于iTRAQ的定量蛋白质组学数据的比较分析显示，参与荚膜多糖合成的几种差异表达蛋白，例如Cps2M，Cps2C，Cps2L，Cps2T，Cps2E和Cps2D ，在D39Δspd1495中被显着上调。随后的透射电子显微镜和糖醛酸检测测定证实，与D39-WT相比，D39Δspd1495中荚膜多糖的合成得到增强。此外，动物研究证实，敲除spd1495会导致荚膜多糖合成增加，以及细菌毒性增加。通过共免疫沉淀测定，表面等离子体共振和电泳迁移率变动测定，我们发现SPD_1495通过与磷酸化ComE（荚膜多糖形成的负转录调节因子）相互作用，负调控cps启动子的表达。总体而言，这项研究表明SPD_1495负调控荚膜多糖的形成，从而增强宿主的细菌毒力。这些发现也为了解这种临床重要细菌的生物学特性提供了宝贵的见识。重要提示荚膜多糖是肺炎链球菌在人类疾病中致病力的关键因素。因此，对荚膜多糖合成的深入了解对于揭示肺炎链球菌感染的发病机理至关重要。在这项研究中，我们表明蛋白质SPD_1495与磷酸化的ComE相互作用，以负调控荚膜多糖的形成。spd1495的删除增加荚膜多糖的合成，从而增强细菌的毒力。这些发现进一步揭示了荚膜多糖的合成机制，并提供了对该临床上重要细菌的生物学的新见解。

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SPD_1495 Contributes to Capsular Polysaccharide Synthesis and Virulence in Streptococcus pneumoniae.

Streptococcus pneumoniae, a Gram-positive human pathogen, causes a series of serious diseases in humans. SPD_1495 from S. pneumoniae is annotated as a hypothetical ABC sugar-binding protein in the NCBI database, but there are few reports on detailed biological functions of SPD_1495. To fully study the influence of SPD_1495 on bacterial virulence in S. pneumoniae, we constructed a deletion mutant (D39Δspd1495) and an overexpressing strain (D39spd1495+). Comparative analysis of iTRAQ-based quantitative proteomic data of the wild-type D39 strain (D39-WT) and D39Δspd1495 showed that several differentially expressed proteins that participate in capsular polysaccharide synthesis, such as Cps2M, Cps2C, Cps2L, Cps2T, Cps2E, and Cps2D, were markedly upregulated in D39Δspd1495 Subsequent transmission electron microscopy and uronic acid detection assay confirmed that capsular polysaccharide synthesis was enhanced in D39Δspd1495 compared to that in D39-WT. Moreover, knockout of spd1495 resulted in increased capsular polysaccharide synthesis, as well as increased bacterial virulence, as confirmed by the animal study. Through a coimmunoprecipitation assay, surface plasmon resonance, and electrophoretic mobility shift assay, we found that SPD_1495 negatively regulated cps promoter expression by interacting with phosphorylated ComE, a negative transcriptional regulator for capsular polysaccharide formation. Overall, this study suggested that SPD_1495 negatively regulates capsular polysaccharide formation and thereby enhances bacterial virulence in the host. These findings also provide valuable insights into understanding the biology of this clinically important bacterium.IMPORTANCE Capsular polysaccharide is a key factor underlying the virulence of Streptococcus pneumoniae in human diseases. Thus, a deep understanding of capsular polysaccharide synthesis is essential for uncovering the pathogenesis of S. pneumoniae infection. In this study, we show that protein SPD_1495 interacts with phosphorylated ComE to negatively regulate the formation of capsular polysaccharide. Deletion of spd1495 increased capsular polysaccharide synthesis and thereby enhanced bacterial virulence. These findings further reveal the synthesis mechanism of capsular polysaccharide and provide new insight into the biology of this clinically important bacterium.

更新日期：2020-02-25

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