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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.

scientific reports

Application of multi-omics technology for the elucidation of anti-pneumococcal activity of 3-acyl-2-phenylamino-1,4-dihydroquinolin-4-one (APDQ) derivative against Streptococcus pneumoniae