Evaluation of L-Alanine Metabolism in Bacteria and Whole-Body Distribution with Bacterial Infection Model Mice
2023
Yuka Muranaka | Miki Matsue | Asuka Mizutani | Masato Kobayashi | Kakeru Sato | Ami Kondo | Yuri Nishiyama | Shusei Ohata | Kodai Nishi | Kana Yamazaki | Ryuichi Nishii | Naoto Shikano | Shigefumi Okamoto | Keiichi Kawai
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<sup>+</sup> dependence, and inhibitory effects using a specific inhibitor of system A. We found that <sup>3</sup>H-L-Ala accurately reflects the proliferative activity of <i>Escherichia coli</i> K-12 and pathogenic EC-14 in vitro. This accumulation in <i>E. coli</i> 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 <sup>3</sup>H-L-Ala showed that the ratio of <sup>3</sup>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.
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