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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Exploring metabolic adaptation of Streptococcus pneumoniae to antibiotics
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Exploring metabolic adaptation of Streptococcus pneumoniae to antibiotics

机译：探索肺炎链球菌肺炎链球菌对抗生素的代谢适应

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摘要

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 TIGR4 Delta cps. For the metabolomics approach, we analyzed the complex variety of metabolites by using H-1 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.
机译：克阳性细菌链球菌肺炎链球菌是社区获得的肺炎，脑膜炎和中耳炎的常见原因之一。分析对环境压力条件的代谢适应改善了我们对其病理生理学的理解及其对宿主衍生营养素的依赖性。在该研究中，评估了特性和细胞内代谢谱，以研究靶向抗菌化合物的影响，靶向S.Pneumoniae TIGR4 Delta CPS的代谢物的不同途径。对于代谢组种方法，我们通过使用H-1 NMR，HPLC-MS和GC-MS作为不同的分析技术分析了复杂的代谢物。通过这种组合，我们检测到近120个代谢物。对于每种抗微生物化合物，检测到常用的单个代谢效应通常包括全球生物合成途径。头孢噻肟改变了氨基酸代谢和碳代谢。嘌呤和嘧啶代谢途径主要受到莫西沙星治疗的影响。与使用单一抗生素的使用相比，头孢噻肟和阿奇霉素的组合强化了应力响应。然而，我们观察到仅通过用两种抗生素的组合治疗来改变三个细胞壁代谢物。只有莫西沙星胁迫引起的CDP-核糖醇浓度的交替。 Teixobactin-Arg10导致肺炎球菌新陈代谢的全局变化。为了满足新抗生素的日益增长的要求，我们的代谢组种方法表明对其他OMICS调查的有希望的补充，允许进入新型抗微生物化合物的作用方式。

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    Leonard Anne; Moehlis Kevin; Schlueter Rabea; Taylor Edward; Lalk Michael; Methling Karen;

  • 作者单位

    Ernst Moritz Arndt Univ Greifswald Inst Biochem Metabol Felix Hausdorff Str 4 D-17489;

    Ernst Moritz Arndt Univ Greifswald Inst Biochem Metabol Felix Hausdorff Str 4 D-17489;

    Ernst Moritz Arndt Univ Greifswald Dept Biol Imaging Ctr FL Jahn Str 15 D-17489 Greifswald;

    Univ Lincoln Sch Life Sci Green Lane Lincoln LN67DL England;

    Ernst Moritz Arndt Univ Greifswald Inst Biochem Metabol Felix Hausdorff Str 4 D-17489;

    Ernst Moritz Arndt Univ Greifswald Inst Biochem Metabol Felix Hausdorff Str 4 D-17489;

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  • 正文语种 eng
  • 中图分类 药学;
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