Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Ochang, 28119, South Korea.
Convergent Research Center for Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, 34114, South Korea.
Sci Rep. 2020 Nov 26;10(1):20685. doi: 10.1038/s41598-020-77694-8.
Streptococcus pneumoniae is one of Gram-positive pathogen that causes invasive pneumococcal disease. Nowadays, many S. pneumoniae strains are resistant to commonly used antibiotics such as β-lactams and macrolides. 3-Acyl-2-phenylamino-1,4-dihydroquinolin-4-one (APDQ) derivatives are known as novel chemicals having anti-pneumococcal activity against S. pneumoniae. The underlying mechanism of the anti-pneumococcal activity of this inhibitor remains unknown. Therefore, we tried to find the anti-pneumococcal mechanism of APDQ230122, one of the APDQ derivatives active against S. pneumoniae. We performed transcriptomic analysis (RNA-Seq) and proteomic analysis (LC-MS/MS analysis) to get differentially expressed genes (DEG) and differentially expressed proteins (DEP) of S. pneumoniae 521 treated with sub-inhibitory concentrations of APDQ230122 and elucidated the comprehensive expression changes of genes and proteins using multi-omics analysis. As a result, genes or proteins of peptidoglycan biosynthesis and DNA replication were significantly down-regulated. Electron microscopy analysis revealed that the structure of peptidoglycan was damaged by APDQ230122 in a chemical concentration-dependent manner. Therefore, we suggest peptidoglycan biosynthesis is a major target of APDQ230122. Multi-omics analysis can provide us useful information to elucidate anti-pneumococcal activity of APDQ230122.
肺炎链球菌是革兰氏阳性病原体之一，可引起侵袭性肺炎球菌病。如今，许多肺炎链球菌菌株对常用抗生素如β-内酰胺类和大环内酯类具有耐药性。3-酰基-2-苯基氨基-1,4-二氢喹啉-4-酮（APDQ）衍生物是一类新型的具有抗肺炎链球菌活性的化学物质。该抑制剂抗肺炎链球菌活性的潜在机制尚不清楚。因此，我们试图寻找 APDQ 衍生物之一 APDQ230122 对肺炎链球菌的抗肺炎机制。我们进行了转录组分析（RNA-Seq）和蛋白质组分析（LC-MS/MS 分析），以获得亚抑制浓度的 APDQ230122 处理的肺炎链球菌 521 的差异表达基因（DEG）和差异表达蛋白（DEP），并使用多组学分析阐明基因和蛋白的综合表达变化。结果表明，肽聚糖生物合成和 DNA 复制的基因或蛋白显著下调。电子显微镜分析显示，APDQ230122 以化学浓度依赖性方式破坏肽聚糖结构。因此，我们认为肽聚糖生物合成是 APDQ230122 的主要靶标。多组学分析可以为阐明 APDQ230122 的抗肺炎活性提供有用信息。
