Exploring metabolic adaptation of Streptococcus pneumoniae to antibiotics

Leonard, Anne, Möhlis, Kevin, Schlüter, Rabea , Taylor, Edward, Lalk, Michael and Methling, Karen (2020) Exploring metabolic adaptation of Streptococcus pneumoniae to antibiotics. The Journal of Antibiotics . pp. 1-14. ISSN 0021-8820

Full content URL: https://doi.org/10.1038/s41429-020-0296-3

Exploring metabolic adaptation of Streptococcus pneumoniae to antibiotics
Open Access published version
etaylor_39.pdf - Whole Document
Available under License Creative Commons Attribution 4.0 International.

Item Type:Article
Item Status:Live Archive


The Gram-positive bacterium Streptococcus pneumoniae is one of the common causes of community acquired pneumonia, meningitis, and otitis media. Analyzing the metabolic adaptation toward environmental stress conditions improves our understanding of its pathophysiology and its dependency on host-derived nutrients. In this study, extra- and intracellular metabolic profiles were evaluated to investigate the impact of antimicrobial compounds targeting different pathways of the metabolome of S. pneumoniae TIGR4Δcps. For the metabolomics approach, we analyzed the complex variety of metabolites by using 1H NMR, HPLC-MS, and GC–MS as different analytical techniques. Through this combination, we detected nearly 120 metabolites. For each antimicrobial compound, individual metabolic effects were detected that often comprised global biosynthetic pathways. Cefotaxime altered amino acids metabolism and carbon metabolism. The purine and pyrimidine metabolic pathways were mostly affected by moxifloxacin treatment. The combination of cefotaxime and azithromycin intensified the stress response compared with the use of the single antibiotic. However, we observed that three cell wall metabolites were altered only by treatment with the combination of the two antibiotics. Only moxifloxacin stress-induced alternation in CDP-ribitol concentration. Teixobactin-Arg10 resulted in global changes of pneumococcal metabolism. To meet the growing requirements for new antibiotics, our metabolomics approach has shown to be a promising complement to other OMICs investigations allowing insights into the mode of action of novel antimicrobial compounds.

Keywords:Streptococcus pneumoniae; Cefotaxime; moxifloxacin; azithromycin; Teixobactin-Arg10
Subjects:C Biological Sciences > C521 Medical Microbiology
C Biological Sciences > C700 Molecular Biology, Biophysics and Biochemistry
C Biological Sciences > C500 Microbiology
Divisions:College of Science > School of Life Sciences
ID Code:40444
Deposited On:06 Apr 2020 10:39

Repository Staff Only: item control page