Gifford Kennedy T L, Pickett Brett E
Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, USA.
Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, USA.
Microb Pathog. 2022 Dec;173(Pt A):105816. doi: 10.1016/j.micpath.2022.105816. Epub 2022 Oct 6.
Infection with Streptococcus pneumoniae causes over 150,000 cases of pneumonia annually in the United States alone. We performed a meta-analysis of publicly available RNA-sequencing data to compare the host-specific intracellular transcriptional responses that differ between infection and carriage with S. pneumoniae in humans and mice. We applied an automated preprocessing workflow to collections of publicly available fastq files that were categorized as either of two phenotypes-infection or carriage in humans and mice. We identified the differentially expressed genes and intracellular signaling pathways that changed in host cells during infection or carriage and whether these human phenotypes could be appropriately modeled at the molecular level in mice. Although we observed multiple differentially expressed genes shared among multiple comparisons, we found no overlapping significant signaling pathways between the mouse and human studies in either phenotype. Based on the samples included in this secondary analysis, we identified a minimal number of generalized transcriptional relationships between host infection and carriage phenotypes of S. pneumoniae that were consistently shared between the mouse and human hosts. Our findings suggest that additional controlled datasets in mouse and human carriage or infection models are needed to better understand the underlying mechanism(s) of invasion and pathogenesis. This knowledge could then contribute to the development of improved prophylactics and/or therapeutics against this pathogen.
仅在美国,每年就有超过15万例肺炎病例是由肺炎链球菌感染引起的。我们对公开可用的RNA测序数据进行了荟萃分析,以比较人类和小鼠在感染肺炎链球菌与携带该菌时宿主特异性细胞内转录反应的差异。我们对公开可用的fastq文件集合应用了自动预处理工作流程,这些文件被分类为两种表型之一——人类和小鼠的感染或携带。我们确定了在感染或携带期间宿主细胞中发生变化的差异表达基因和细胞内信号通路,以及这些人类表型在小鼠中是否能在分子水平上得到适当模拟。尽管我们在多次比较中观察到多个共享的差异表达基因,但在两种表型的小鼠和人类研究中,我们均未发现重叠的显著信号通路。基于本次二次分析中纳入的样本,我们确定了肺炎链球菌宿主感染和携带表型之间最少数量的普遍转录关系,这些关系在小鼠和人类宿主中是一致共享的。我们的研究结果表明,需要在小鼠和人类携带或感染模型中获取更多对照数据集,以更好地了解侵袭和发病机制的潜在机制。这些知识随后可能有助于开发针对这种病原体的改进型预防措施和/或治疗方法。