Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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A Novel Truncated CHAP Modular Endolysin, CHAPSAP26-161, That Lyses Staphylococcus aureus, Acinetobacter baumannii, and Clostridioides difficile, and Exhibits Therapeutic Effects in a Mouse Model of A. baumannii Infection

  • Yoon-Jung Choi (Department of Microbiology, School of Medicine, Kyungpook National University) ;
  • Shukho Kim (Department of Microbiology, School of Medicine, Kyungpook National University) ;
  • Ram Hari Dahal (Department of Microbiology, School of Medicine, Kyungpook National University) ;
  • Jungmin Kim (Department of Microbiology, School of Medicine, Kyungpook National University)
  • Received : 2024.02.23
  • Accepted : 2024.05.29
  • Published : 2024.08.28
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Abstract

Development of novel antibacterial agents is imperative due to the increasing threat of antibiotic-resistant pathogens. This study aimed to develop the enhanced antibacterial activity and in-vivo efficacy of a novel truncated endolysin, CHAPSAP26-161, derived from the endolysin LysSAP26, against multidrug-resistant bacteria. CHAPSAP26-161 exhibited higher protein purification efficiency in E. coli and antibacterial activity than LysSAP26. Moreover, CHAPSAP26-161 showed the higher lytic activity against A. baumannii with minimal bactericidal concentrations (MBCs) of 5-10 ㎍/ml, followed by Staphylococcus aureus with MBCs of 10-25 ㎍/ml. Interestingly, CHAPSAP26-161 could lyse anaerobic bacteria, such as Clostridioides difficile, with MBCs of 25-50 ㎍/ml. At pH 4-8 and temperatures of 4℃-45℃, CHAPSAP26-161 maintained antibacterial activity without remarkable difference. The lytic activity of CHAPSAP26-161 was increased with Zn2+. In vivo tests demonstrated the therapeutic effects of CHAPSAP26-161 in murine systemic A. baumannii infection model. In conclusion, CHAPSAP26-161, a truncated endolysin that retains only the CHAP domain from LysSAP26, demonstrated enhanced protein purification efficiency and antibacterial activity compared to LysSAP26. It further displayed broad-spectrum antibacterial effects against S. aureus, A. baumannii, and C. difficile. Our in vitro and in-vivo results of CHAPSAP26-161 highlights its promise as an innovative therapeutic option against those bacteria with multiple antibiotic resistance.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Education and the Korea government Ministry of Science and ICT (MSIT), grant numbers NRF-2017R1D1A3-B06032486 and NRF-2022R1F1A1073686, respectively.

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