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

• Published in: International journal of molecular sciences Vol. 24; no. 5; p. 4775
• Main Authors: Muranaka, Yuka, Matsue, Miki, Mizutani, Asuka, Kobayashi, Masato, Sato, Kakeru, Kondo, Ami, Nishiyama, Yuri, Ohata, Shusei, Nishi, Kodai, Yamazaki, Kana, Nishii, Ryuichi, Shikano, Naoto, Okamoto, Shigefumi, Kawai, Keiichi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.03.2023; MDPI
• Subjects: Accumulation; Alanine; Alanine - metabolism; Amino acids; Amino Acids - metabolism; Animal models; Animals; Antimicrobial resistance; Bacteria; bacterial imaging; bacterial infection; Bacterial Infections; Cancer; E coli; Escherichia coli; Escherichia coli - metabolism; Escherichia coli K12 - metabolism; Health aspects; Humans; Infections; Infectious diseases; L-Alanine; Mice; Muscles; nuclear medicine imaging; Pathogens; Physiological aspects; Transportation systems; Tumor cells; Japan; bacterial imaging; alanine; nuclear medicine imaging; bacterial infection; amino acids
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24054775

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.