Research Centre for Infectious Diseases, Department of Molecular and Biomedical Science, University of Adelaide, Adelaide, 5005, Australia.
Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, 1015, Lausanne, Switzerland.
Commun Biol. 2020 Jun 5;3(1):293. doi: 10.1038/s42003-020-1018-x.
Streptococcus pneumoniae is a genetically diverse human-adapted pathogen commonly carried asymptomatically in the nasopharynx. We have recently shown that a single nucleotide polymorphism (SNP) in the raffinose pathway regulatory gene rafR accounts for a difference in the capacity of clonally-related strains to cause localised versus systemic infection. Using dual RNA-seq, we show that this SNP affects expression of bacterial genes encoding multiple sugar transporters, and fine-tunes carbohydrate metabolism, along with extensive rewiring of host transcriptional responses to infection, particularly expression of genes encoding cytokine and chemokine ligands and receptors. The data predict a crucial role for differential neutrophil recruitment (confirmed by in vivo neutrophil depletion and IL-17 neutralization) indicating that early detection of bacteria by the host in the lung environment is crucial for effective clearance. Thus, dual RNA-seq provides a powerful tool for understanding complex host-pathogen interactions and reveals how a single bacterial SNP can drive differential disease outcomes.
肺炎链球菌是一种遗传多样性的人类病原体，通常无症状地存在于鼻咽部。我们最近发现，岩藻糖途径调节基因 rafR 中的单个核苷酸多态性 (SNP) 导致了具有密切亲缘关系的菌株引起局部感染与全身感染的能力的差异。通过双 RNA-seq，我们表明该 SNP 影响了编码多种糖转运蛋白的细菌基因的表达，并微调了碳水化合物代谢，同时对感染的宿主转录反应进行了广泛的重新布线，特别是细胞因子和趋化因子配体和受体的基因表达。这些数据预测了差异中性粒细胞募集的关键作用（通过体内中性粒细胞耗竭和 IL-17 中和来证实），表明宿主在肺部环境中对细菌的早期检测对于有效清除至关重要。因此，双 RNA-seq 为理解复杂的宿主-病原体相互作用提供了强大的工具，并揭示了单个细菌 SNP 如何导致不同的疾病结局。
