2. Academic Validation
  3. Development of a small compound that regulates the function of a maltodextrin-binding protein of Streptococcus pyogenes by multifaceted screenings

Development of a small compound that regulates the function of a maltodextrin-binding protein of Streptococcus pyogenes by multifaceted screenings

  • Sci Rep. 2025 Jun 2;15(1):19341. doi: 10.1038/s41598-025-02175-9.
Tsukushi Yamawaki 1,  Makoto Nakakido 2 3,  Satoru Nagatoishi 1 4 5,  Jose M M Caaveiro 6,  Daisuke Kuroda 4 7,  Chihiro Aikawa 8,  Ichiro Nakagawa 9,  Kouhei Tsumoto 10 11 12 13
Affiliations

Affiliations

  • 1 Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8656, Japan.
  • 2 Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8656, Japan. nakakido@g.ecc.u-tokyo.ac.jp.
  • 3 Department of Bioengineering, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8656, Japan. nakakido@g.ecc.u-tokyo.ac.jp.
  • 4 Department of Bioengineering, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8656, Japan.
  • 5 Medical Device Development and Regulation Research Center, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8656, Japan.
  • 6 Department of Protein Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
  • 7 Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-Ku, Tokyo, 162-8640, Japan.
  • 8 Section of Applied Veterinary Sciences, Division of Veterinary Sciences, Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido, 080-8555, Japan.
  • 9 Department of Microbiology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-Cho, Sakyo-Ku, Kyoto, 606-8501, Japan.
  • 10 Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8656, Japan. tsumoto@bioeng.t.u-tokyo.ac.jp.
  • 11 Department of Bioengineering, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8656, Japan. tsumoto@bioeng.t.u-tokyo.ac.jp.
  • 12 Medical Device Development and Regulation Research Center, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8656, Japan. tsumoto@bioeng.t.u-tokyo.ac.jp.
  • 13 Medical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, Minato-Ku, Tokyo, 108-8639, Japan. tsumoto@bioeng.t.u-tokyo.ac.jp.
PMID: 40456803 DOI: 10.1038/s41598-025-02175-9
Abstract

Group A Streptococcus (GAS) are gram-positive bacteria that cause various symptoms. The treatment of GAS infections currently relies on Antibiotics, but new treatment options are needed due to the spread of Antibiotic resistance. To develop novel treatment methods that circumvent the generation of Antibiotic resistance, we used virtual screening followed by several biophysical-based screening methods to identify Antibacterial compounds that target SPs0871, which is a maltodextrin-binding protein that is involved in carbohydrate catabolism in GAS. We narrowed down the list of compounds in the library via multi-step screening and finally isolated a compound that bacteriostatically inhibited the growth of GAS. Together with our previous study showing that an anti-SPs0871 variable heavy domain of heavy chain antibody, which completely blocked ligand binding, did not suppress Bacterial growth, our results provide guidelines for designing an antistreptococcal therapeutic.

Keywords

Streptococcus pyogenes; Accessibility; Antimicrobial resistance; Maltose/maltodextrin-binding protein; Small compound; Target based screening.

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