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한빛사논문

조회321

조영진Youngjin Cho

아주대학교

Int. J. Antimicrob. Agents, May 27 2024, S0924-8579(24)00140-7 | https://doi.org/10.1016/j.ijantimicag.2024.107222 Exploring the therapeutic potential of endolysin CD27L_EAD against Clostridioides difficile infection

Youngjin Cho^a, Kyungah Park ^a, Jeongseok Park ^a, Jieun An ^a, Heejoon Myung ^b,c, Hyunjin Yoon ^a,d

^aDepartment of Molecular Science and Technology, Ajou University, Suwon, South Korea

^bLyseNTech Co., Ltd., Seongnam, South Korea

^cDepartment of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yongin, South Korea

^dDepartment of Applied Chemistry and Biological Engineering, Ajou University, Suwon, South Korea

Corresponding author: Hyunjin Yoon

Abstract

Clostridioides difficile has emerged as a major cause of life-threatening diarrheal disease. Conventional antibiotics used in current standards of care exacerbate the emergence of antibiotic-resistant strains and pose a risk of recurrent C. difficile infection (CDI). Thus, there is an urgent need for alternative therapeutics that selectively eliminate C. difficile without disturbing the commensal microbiota. Endolysin is a bacteriophage-derived peptidoglycan hydrolase that aids in the release of phage progeny during the final stage of infection. In order to exploit endolysin as a therapeutic agent against CDI, the bactericidal activity of 23 putative endolysins was compared and ΦCD27 endolysin CD27L was selected and modified to CD27L_EAD by cleaving the cell-wall binding domain of CD27L. CD27L_EAD exhibited greater bacteriolytic activity than CD27L and its activity was stable over a wide range of salt concentrations and pH conditions. CD27L_EAD was added to a co-culture of human gut microbiota with C. difficile and the bacterial community structure was analyzed. CD27L_EAD did not impair the richness and diversity of the bacterial population but remarkably attenuated the abundance of C. difficile. Furthermore, the co-administration of vancomycin exerted synergistic bactericidal activity against C. difficile. β-diversity analysis revealed that CD27L_EAD did not significantly disturb the composition of the microbial community, whereas the abundance of some species belonging to the family Lachnospiraceae decreased after CD27L_EAD treatment. This study provides insights into endolysin as a prospective therapeutic agent for the treatment of CDI without damaging the normal gut microbiota.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-05-31)
연구진국내 연구진
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