Pettersen Jens Sivkær, Høg Frida Fabricius, Nielsen Flemming Damgaard, Møller-Jensen Jakob, Jørgensen Mikkel Girke
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
Front Microbiol. 2022 Dec 21;13:1060583. doi: 10.3389/fmicb.2022.1060583. eCollection 2022.
(pneumococcus) is a leading cause of severe invasive infectious diseases such as sepsis and meningitis. Understanding how pneumococcus adapts and survive in the human bloodstream environment and cerebrospinal fluid (CSF) is important for development of future treatment strategies. This study investigates the global transcriptional response of pneumococcus to human blood components and CSF acquired from discarded and anonymized patient samples. Extensive transcriptional changes to human blood components were observed during early stages of interaction. Plasma-specific responses were primarily related to metabolic components and include strong downregulation of fatty acid biosynthesis genes, and upregulation of nucleotide biosynthesis genes. No transcriptional responses specific to the active plasma proteins (e.g., complement proteins) were observed during early stages of interaction as demonstrated by a differential expression analysis between plasma and heat-inactivated plasma. The red blood cell (RBC)-specific response was far more complex, and included activation of the competence system, differential expression of several two-component systems, phosphotransferase systems and transition metal transporter genes. Interestingly, most of the changes observed for CSF were also observed for plasma. One of the few CSF-specific responses, not observed for plasma, was a strong downregulation of the iron acquisition system . Intriguingly, this transcriptomic analysis also uncovers significant differential expression of more than 20 small non-coding RNAs, most of them in response to RBCs, including small RNAs from uncharacterized type I toxin-antitoxin systems. In summary, this transcriptomic study identifies key pneumococcal metabolic pathways and regulatory genes involved with adaptation to human blood and CSF. Future studies should uncover the potential involvement of these factors with virulence .
肺炎球菌是败血症和脑膜炎等严重侵袭性传染病的主要病因。了解肺炎球菌如何在人体血液环境和脑脊液（CSF）中适应并存活，对于未来治疗策略的制定至关重要。本研究调查了肺炎球菌对从废弃且匿名的患者样本中获取的人体血液成分和脑脊液的全局转录反应。在相互作用的早期阶段观察到了对人体血液成分的广泛转录变化。血浆特异性反应主要与代谢成分有关，包括脂肪酸生物合成基因的强烈下调和核苷酸生物合成基因的上调。如血浆与热灭活血浆之间的差异表达分析所示，在相互作用的早期阶段未观察到对活性血浆蛋白（如补体蛋白）的特异性转录反应。红细胞（RBC）特异性反应则更为复杂，包括感受态系统的激活、几个双组分系统、磷酸转移酶系统和过渡金属转运蛋白基因的差异表达。有趣的是，在脑脊液中观察到的大多数变化在血浆中也有观察到。少数脑脊液特异性反应之一（血浆中未观察到）是铁摄取系统的强烈下调。耐人寻味的是，这种转录组分析还揭示了20多种小非编码RNA的显著差异表达，其中大多数是对红细胞的反应，包括来自未表征的I型毒素-抗毒素系统的小RNA。总之，这项转录组研究确定了肺炎球菌参与适应人体血液和脑脊液的关键代谢途径和调控基因。未来的研究应揭示这些因素与毒力的潜在关联。
