Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, South Australia, Australia.
PLoS One. 2013 Aug 13;8(8):e70862. doi: 10.1371/journal.pone.0070862. eCollection 2013.
To date, the role of transcription factors (TFs) in the progression of disease for many pathogens is yet to be studied in detail. This is probably due to transient, and generally low expression levels of TFs, which are the central components controlling the expression of many genes during the course of infection. However, a small change in the expression or specificity of a TF can radically alter gene expression. In this study, we combined a number of quality-based selection strategies including structural prediction of modulated genes, gene ontology and network analysis, to predict the regulatory mechanisms underlying pathogenesis of Streptococcus pneumoniae (the pneumococcus). We have identified two TFs (SP_0676 and SP_0927 [SmrC]) that might control tissue-specific gene expression during pneumococcal translocation from the nasopharynx to lungs, to blood and then to brain of mice. Targeted mutagenesis and mouse models of infection confirmed the role of SP_0927 in pathogenesis and virulence, and suggests that SP_0676 might be essential to pneumococcal viability. These findings provide fundamental new insights into virulence gene expression and regulation during pathogenesis.
迄今为止，许多病原体疾病进展过程中转录因子（TFs）的作用尚未得到详细研究。这可能是由于 TFs 的表达通常是短暂的和低水平的，它们是在感染过程中控制许多基因表达的核心组成部分。然而，TF 的表达或特异性的微小变化可以彻底改变基因表达。在这项研究中，我们结合了多种基于质量的选择策略，包括调节基因的结构预测、基因本体论和网络分析，以预测肺炎链球菌（肺炎球菌）发病机制的调节机制。我们已经确定了两个 TFs（SP_0676 和 SP_0927[SmrC]），它们可能在肺炎球菌从鼻咽部转移到肺部、血液和大脑的过程中控制组织特异性基因表达。靶向诱变和感染小鼠模型证实了 SP_0927 在发病机制和毒力中的作用，并表明 SP_0676 可能对肺炎球菌的生存能力至关重要。这些发现为发病机制过程中的毒力基因表达和调控提供了基本的新见解。
