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Exploring the therapeutic potential of endolysin CD27L_EAD against Clostridioides difficile infection.
- Source :
-
International journal of antimicrobial agents [Int J Antimicrob Agents] 2024 Aug; Vol. 64 (2), pp. 107222. Date of Electronic Publication: 2024 May 27. - Publication Year :
- 2024
-
Abstract
- Objectives: 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. This study aimed to explore the potential of endolysins as an alternative therapeutic agent to antibiotics. Endolysin is a bacteriophage-derived peptidoglycan hydrolase that aids in the release of phage progeny during the final stage of infection.<br />Methods: 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&#95;EAD by cleaving the cell-wall binding domain of CD27L.<br />Results: CD27L&#95;EAD exhibited greater bacteriolytic activity than CD27L and its activity was stable over a wide range of salt concentrations and pH conditions. CD27L&#95;EAD was added to a co-culture of human gut microbiota with C. difficile and the bacterial community structure was analyzed. CD27L&#95;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&#95;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&#95;EAD treatment.<br />Conclusions: This study provides insights into endolysin as a prospective therapeutic agent for the treatment of CDI without damaging the normal gut microbiota.<br /> (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Subjects :
- Humans
Gastrointestinal Microbiome drug effects
Bacteriophages genetics
Bacteriolysis drug effects
Clostridioides difficile drug effects
Clostridioides difficile genetics
Endopeptidases pharmacology
Endopeptidases genetics
Endopeptidases therapeutic use
Clostridium Infections drug therapy
Clostridium Infections microbiology
Anti-Bacterial Agents pharmacology
Anti-Bacterial Agents therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7913
- Volume :
- 64
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- International journal of antimicrobial agents
- Publication Type :
- Academic Journal
- Accession number :
- 38810936
- Full Text :
- https://doi.org/10.1016/j.ijantimicag.2024.107222