Assessing the feasibility of employing a combination of a bacteriophage-derived endolysin and spore germinants to treat relapsing clostridioides difficile infection

Alyahya, Khalid and Baillie, Les ORCID: https://orcid.org/0000-0002-8186-223X 2023. Assessing the feasibility of employing a combination of a bacteriophage-derived endolysin and spore germinants to treat relapsing clostridioides difficile infection. Microorganisms 11 (7) , 1651. 10.3390/microorganisms11071651

PDF - Published Version Available under License Creative Commons Attribution. Download (3MB)

Abstract

Clostridioides difficile is a Gram-positive, anaerobic, spore-forming bacillus and is a major cause of healthcare-associated infections. Whereas the vegetative form of the pathogen is susceptible to treatment with antibiotics, its ability to persist in the gut as antibiotic-resistant spores means that reinfection can occur in cases were the individual fails to re-establish a protective microflora. Bacteriophages and their lysins are currently being explored as treatment options due to their specificity, which minimizes the disruption to the other members of the gut microflora that are protective. The feasibility of employing recombinant endolysins to target the vegetative form of C. difficile has been demonstrated in animal models. In this study, we cloned and expressed the enzyme active domain of LysCD6356 and confirmed its ability to lyse the vegetative forms of a diverse range of clinical isolates of C. difficile, which included members of the hypervirulent 027 ribotype. Lytic activity was adversely affected by calcium, which is naturally found in the gut and is released from the spore upon germination. Our results suggests that a strategy in which the triggering of spore germination is separated in time from the application of the lysin could be developed as a strategy to reduce the risk of relapsing C. difficile infections.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Pharmacy
Additional Information:	License information from Publisher: LICENSE 1: URL: https://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	MDPI
Date of First Compliant Deposit:	10 July 2023
Date of Acceptance:	20 June 2023
Last Modified:	11 Jul 2023 04:31
URI:	https://orca.cardiff.ac.uk/id/eprint/160892

Actions (repository staff only)

Edit Item