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评估细菌中的 L-丙氨酸代谢和细菌感染模型小鼠的全身分布。

Evaluation of L-Alanine Metabolism in Bacteria and Whole-Body Distribution with Bacterial Infection Model Mice.

机构信息

Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Japan.

Ishikawa Prefectural Institute of Public Health and Environmental Science, 1-11 Taiyogaoka, Kanazawa 920-1154, Japan.

出版信息

Int J Mol Sci. 2023 Mar 1;24(5):4775. doi: 10.3390/ijms24054775.

Abstract

The World Health Organization has cautioned that antimicrobial resistance (AMR) will be responsible for an estimated 10 million deaths annually by 2050. To facilitate prompt and accurate diagnosis and treatment of infectious disease, we investigated the potential of amino acids for use as indicators of bacterial growth activity by clarifying which amino acids are taken up by bacteria during the various growth phases. In addition, we examined the amino acid transport mechanisms that are employed by bacteria based on the accumulation of labeled amino acids, Na dependence, and inhibitory effects using a specific inhibitor of system A. We found that H-L-Ala accurately reflects the proliferative activity of K-12 and pathogenic EC-14 in vitro. This accumulation in could be attributed to the amino acid transport systems being different from those found in human tumor cells. Moreover, biological distribution assessed in infection model mice with EC-14 using H-L-Ala showed that the ratio of H-L-Ala accumulated in infected muscle to that in control muscle was 1.20. By detecting the growth activity of bacteria in the body that occurs during the early stages of infection by nuclear imaging, such detection methods may result in expeditious diagnostic treatments for infectious diseases.

摘要

世界卫生组织警告称,到 2050 年,抗菌药物耐药性(AMR)每年将导致约 1000 万人死亡。为了促进传染病的快速准确诊断和治疗,我们通过阐明细菌在不同生长阶段中摄取哪些氨基酸,研究了氨基酸作为细菌生长活性指标的潜力。此外,我们还研究了基于标记氨基酸的积累、Na 依赖性以及使用特定的系统 A 抑制剂的抑制作用的细菌氨基酸转运机制。我们发现 H-L-Ala 准确反映了 K-12 和致病性 EC-14 在体外的增殖活性。这种在 中的积累可以归因于氨基酸转运系统与人类肿瘤细胞中的不同。此外,使用 H-L-Ala 在感染模型小鼠中对 EC-14 进行的生物分布评估表明,感染肌肉中积累的 H-L-Ala 与对照肌肉中的比值为 1.20。通过核成像检测感染早期体内细菌的生长活性,这种检测方法可能会加速传染病的诊断和治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0243/10002749/49ae74ccd29b/ijms-24-04775-g001.jpg

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