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2024 Vol.54, Issue 2 Preview Page

Original Article

CHAPSAP26-161, A Truncated Protein and Enzymatic Active Domain of Endolysin LysSAP26, as a Potential Therapeutic Agent to Combat Clostridioides difficile Infection
Ram Hari Dahal1†
,
Yoon-Jung Choi1†
,
Shukho Kim1
,
Jungmin Kim1*
1Department of Microbiology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
*minkim@knu.ac.kr
†These authors have contributed equally to this work and are co-first authors.
30 June 2024. pp. 107-121
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Abstract

Clostridioides difficile is a spore-forming enteric pathogen that causes life-threatening diarrhea and colitis. Notably, C. difficile infection (CDI) is a major healthcare-associated infection with increasing incidence and morbidity rates. Antibiotic-induced microbial disruption has been linked to susceptibility to CDI transmission and relapse. Therefore, alternative therapeutic approaches that effectively prevent C. difficile growth and spore germination are urgently needed. Bacteriophage-derived endolysins and their derivatives have recently shown potential as novel antibacterial agents. Hence, this study aimed to investigate the efficacy of a novel truncated cysteine-histidine-dependent amidohydrolase/peptidase (CHAP) modular endolysin, CHAPSAP26-161, in combating CDI. In vitro studies demonstrated its potent bactericidal activity against several clinically relevant C. difficile strains, including toxin A- and toxin B-producing and nontoxigenic strains. CHAPSAP26-161 exhibited rapid and specific killing activity, thereby significantly reducing C. difficile colony-forming units. Furthermore, in a murine CDI model, CHAPSAP26-161 treatment remarkably reduced C. difficile burden and clinical symptoms, such as diarrhea and weight loss. In histopathological analysis, colonic inflammation and tissue damage decreased in CHAPSAP26-161-treated mice compared with that in the control group. Moreover, no cytotoxic effects were observed on the A549 cell line, indicating that CHAPSAP26-161 is safe as a therapeutic agent. These findings highlight that CHAPSAP26-161 is a promising treatment option for CDI. Importantly, preclinical and clinical studies are warranted to fully evaluate the therapeutic potential of CHAPSAP26-161 and its possible implementation in clinical practice.

Keywords
Endolysin
Clostridioides difficile infection (CDI)
Alternatives antibiotics
Colonic inflammation
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Information
  • Publisher :The Korean Society for Microbiology and The Korean Society of Virology
  • Publisher(Ko) :대한미생물학회‧대한바이러스학회
  • Journal Title :JOURNAL OF BACTERIOLOGY AND VIROLOGY
  • Volume : 54
  • No :2
  • Pages :107-121
  • Received Date : 2024-04-26
  • Revised Date : 2024-06-04
  • Accepted Date : 2024-06-10
  • DOI :https://doi.org/10.4167/jbv.2024.54.2.107
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