Department of Respiratory Sciences, University of Leicestergrid.9918.9, Leicester, United Kingdom.
Department of Medical Laboratory Science, College of Medicals and Applied Sciences, University of Charmo, Chamchamal, Iraq.
Infect Immun. 2021 Nov 16;89(12):e0040021. doi: 10.1128/IAI.00400-21. Epub 2021 Sep 7.
During its progression from the nasopharynx to other sterile and nonsterile niches of its human host, Streptococcus pneumoniae must cope with changes in temperature. We hypothesized that the temperature adaptation is an important facet of pneumococcal survival in the host. Here, we evaluated the effect of temperature on pneumococcus and studied the role of glutamate dehydrogenase (GdhA) in thermal adaptation associated with virulence and survival. Microarray analysis revealed a significant transcriptional response to changes in temperature, affecting the expression of 252 genes in total at 34°C and 40°C relative to at 37°C. One of the differentially regulated genes was which is upregulated at 40°C and downregulated at 34°C relative to 37°C. Deletion of attenuated the growth, cell size, biofilm formation, pH survival, and biosynthesis of proteins associated with virulence in a temperature-dependent manner. Moreover, deletion of stimulated formate production irrespective of temperature fluctuation. Finally, Δ grown at 40°C was less virulent than other temperatures or the wild type at the same temperature in a Galleria mellonella infection model, suggesting that GdhA is required for pneumococcal virulence at elevated temperature.
在从鼻咽部向其人类宿主的其他无菌和非无菌小生境传播的过程中,肺炎链球菌必须应对温度变化。我们假设温度适应是肺炎链球菌在宿主中存活的一个重要方面。在这里,我们评估了温度对肺炎链球菌的影响,并研究了谷氨酸脱氢酶(GdhA)在与毒力和存活相关的热适应中的作用。微阵列分析显示,温度变化会引起明显的转录反应,导致在 34°C 和 40°C 时相对于 37°C 时总共调节 252 个基因的表达。其中一个差异调节的基因是 ,其在 40°C 时上调,在 34°C 时下调,相对于 37°C。与 37°C 相比,Δ 的缺失以温度依赖的方式减弱了生长、细胞大小、生物膜形成、pH 存活和与毒力相关的蛋白质的生物合成。此外,无论温度波动如何,Δ 的缺失都会刺激甲酸盐的产生。最后,在金斑蝶感染模型中,在 40°C 下生长的 Δ 比其他温度或相同温度下的野生型的毒力更低,这表明 GdhA 是肺炎链球菌在高温下毒力所必需的。