Metabolomics Reveal D-Alanine:D-Alanine Ligase As the Target of D-Cycloserine in Mycobacterium tuberculosis
文献类型：期刊论文
| 作者 | Prosser, G. A. |
| 刊名 | Acs Medicinal Chemistry Letters
 |
| 出版日期 | 2013 |
| 卷号 | 4期号:12页码:1233-1237 |
| ISSN号 | 1948-5875 |
| 中文摘要 | Stable isotope-mass spectrometry (MS)-based metabolomic profiling is a powerful technique for following changes in specific metabolite pool sizes and metabolic flux under various experimental conditions in a test organism or cell type. Here, we use a metabolomics approach to interrogate the mechanism of antibiotic action of D-cycloserine (DCS), a second line antibiotic used in the treatment of multidrug resistant Mycobacterium tuberculosis infections. We use doubly labeled C-13 alpha-carbon H-2 L-alanine to allow tracking of both alanine racemase and D-alanine:D-alanine ligase activity in M. tuberculosis challenged with DCS and reveal that D-alanine:D-alanine ligase is more strongly inhibited than alanine racemase at equivalent DCS concentrations. We also shed light on mechanisms surrounding D-Ala-mediated antagonism of DCS growth inhibition and provide evidence for a postantibiotic effect for this drug. Our results illustrate the potential of metabolomics in cellular drug-target engagement studies and consequently have broad implications in future drug development and target validation ventures. |
| 公开日期 | 2015-03-27 |
| 源URL | [http://ir.xtbg.org.cn/handle/353005/8495]  |
| 专题 | 西双版纳热带植物园_公共技术服务中心主要仪器相关文献_同位素质谱仪 |
| 推荐引用方式 GB/T 7714 | Prosser, G. A.. Metabolomics Reveal D-Alanine:D-Alanine Ligase As the Target of D-Cycloserine in Mycobacterium tuberculosis[J]. Acs Medicinal Chemistry Letters,2013,4(12):1233-1237. |
| APA | Prosser, G. A..(2013).Metabolomics Reveal D-Alanine:D-Alanine Ligase As the Target of D-Cycloserine in Mycobacterium tuberculosis.Acs Medicinal Chemistry Letters,4(12),1233-1237. |
| MLA | Prosser, G. A.."Metabolomics Reveal D-Alanine:D-Alanine Ligase As the Target of D-Cycloserine in Mycobacterium tuberculosis".Acs Medicinal Chemistry Letters 4.12(2013):1233-1237. |
入库方式： OAI收割
来源：西双版纳热带植物园
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