The involvement of CiaR and the CiaR-regulated serine protease HtrA in thermal adaptation of Streptococcus pneumoniae.

The involvement of CiaR and the CiaR-regulated serine protease HtrA in thermal adaptation of Streptococcus pneumoniae.
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DOI:
10.1099/mic.0.001304
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发表时间:
2023-02
期刊:
影响因子:
2.8
通讯作者:
Yesilkaya, Hasan
Yesilkaya, Hasan
中科院分区:
生物学4区
文献类型:
--
作者:
Gazioglu, Ozcan;Habtom, Medhanie;Andrew, Peter W.;Yesilkaya, Hasan

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体内温度可以根据宿主组织和对感染的反应而变化。肺炎链球菌已经进化出存活这些温度差异的机制,但不同温度对肺炎球菌表型的影响和热适应的遗传基础都不清楚。在我们之前的研究中,我们发现Ciar是双组分调节系统CiaRH的一部分,以及17个已知受CiaRH控制的基因,被鉴定为随温度差异表达。CiaRH调控的受温度差异调控的基因之一是高温需求蛋白(HtrA),由Spd_2068(HtrA)编码。在这项研究中,我们假设CiaRH系统通过控制htrA在肺炎球菌热适应中发挥重要作用。这一假说是通过在体外和体内测试突变或过度表达Ciar和/或htrA的菌株来评估的。结果表明,在没有CIAR的情况下,仅在40 °C时,HtrA的生长、溶血活性、被膜数量和生物膜的形成都显著降低,而在34和40 °C时细胞的大小和毒力都受到影响。htrA在∆CIAR背景中的过表达重建了所有温度下的生长,而∆Ciar在40 °C时部分地溶血活性、生物膜形成和毒力。另外,在40 °C时,htrA在野生型中的过表达促进了肺炎链球菌的毒力,而在34 °C时,观察到了衣壳的增加,这表明htrA的作用在不同的温度下发生了变化。我们的数据表明,Ciar和HtrA在肺炎球菌热适应中起着重要作用。
The in vivo temperature can vary according to the host tissue and the response to infection. Streptococcus pneumoniae has evolved mechanisms to survive these temperature differences, but neither the consequences of different temperatures for pneumococcal phenotype nor the genetic basis of thermal adaptation are known in detail. In our previous study, we found that CiaR, which is a part of two-component regulatory system CiaRH, as well as 17 genes known to be controlled by CiaRH, were identified to be differentially expressed with temperature. One of the CiaRH-regulated genes shown to be differentially regulated by temperature is for the high-temperature requirement protein (HtrA), coded by SPD_2068 (htrA). In this study, we hypothesized that the CiaRH system plays an important role in pneumococcal thermal adaptation through its control over htrA. This hypothesis was evaluated by testing strains mutated or overexpressing ciaR and/or htrA, in in vitro and in vivo assays. The results showed that in the absence of ciaR, the growth, haemolytic activity, amount of capsule and biofilm formation were considerably diminished at 40 °C only, while the cell size and virulence were affected at both 34 and 40 °C. The overexpression of htrA in the ∆ciaR background reconstituted the growth at all temperatures, and the haemolytic activity, biofilm formation and virulence of ∆ciaR partially at 40 °C. We also showed that overexpression of htrA in the wild-type promoted pneumococcal virulence at 40 °C, while the increase of capsule was observed at 34 °C, suggesting that the role of htrA changes at different temperatures. Our data suggest that CiaR and HtrA play an important role in pneumococcal thermal adaptation.
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