Detection of Bacteria-Specific Metabolism Using Hyperpolarized [2-13C]Pyruvate,ACS Infectious Diseases

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Detection of Bacteria-Specific Metabolism Using Hyperpolarized [2-13C]Pyruvate
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2018-02-06 00:00:00 , DOI: 10.1021/acsinfecdis.7b00234
Renuka Sriram ₁ , Jinny Sun ₁ , Javier Villanueva-Meyer ₁ , Christopher Mutch ₁ , Justin De Los Santos ₁ , Jason Peters ₂ , David E. Korenchan ₁ , Kiel Neumann ₃ , Mark Van Criekinge ₁ , John Kurhanewicz ₁ , Oren Rosenberg ₄ , David Wilson ₁ , Michael A. Ohliger _{1,

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Affiliation

The differentiation of bacterial infection from other causes of inflammation is difficult in clinical practice and is critical where patient outcomes rely heavily on early interventions. In addition to physical exam and laboratory markers, several imaging modalities are frequently employed, but these techniques generally target the host immune response, rather than the living microorganisms themselves. Here, we describe a method to detect bacteria-specific metabolism using hyperpolarized (HP) ¹³C magnetic resonance spectroscopy. This technology allows visualization of the real-time conversion of enriched ¹³C substrates to their metabolic products, identified by their distinct chemical shifts. We have identified the rapid metabolism of HP [2-¹³C]pyruvate to [1-¹³C]acetate as a metabolic signature of common bacterial pathogens. We demonstrate this conversion in representative Gram-negative and Gram-positive bacteria, namely, Escherichia coli and Staphylococcus aureus, and its absence in key mammalian cell types. Furthermore, this conversion was successfully modulated in three mutant strains, corresponding to deletions of relevant enzymes.

中文翻译：

使用超极化[2- ¹³ C]丙酮酸检测细菌特定的代谢

在临床实践中，很难将细菌感染与其他炎症原因区分开来，并且在患者结果严重依赖早期干预的情况下至关重要。除了体格检查和实验室标记外，还经常使用几种成像方式，但是这些技术通常针对宿主的免疫反应，而不是针对活微生物本身。在这里，我们描述了一种使用超极化（HP）¹³ C磁共振波谱检测细菌特异性代谢的方法。这项技术可以可视化实时显示富集的¹³ C底物向其代谢产物的实时转化，并通过其独特的化学位移进行识别。我们已经确定了HP的快速代谢[2- ¹³C]丙酮酸至[1- ¹³ C]乙酸盐作为常见的细菌性病原体代谢签名。我们证明了这种转化在代表性的革兰氏阴性和革兰氏阳性细菌中，即大肠杆菌和金黄色葡萄球菌，在关键的哺乳动物细胞类型中不存在。此外，在三种突变菌株中成功地调节了这种转化，对应于相关酶的缺失。

更新日期：2018-02-06

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