Assessing the Feasibility of Employing a Combination of a Bacteriophage-Derived Endolysin and Spore Germinants to Treat Relapsing Clostridioides difficile Infection

Author:

Alyahya Khalid12ORCID,Baillie Les2

Affiliation:

1. Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

2. School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3NB, UK

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.

Funder

King Saud University

Publisher

MDPI AG

Subject

Virology,Microbiology (medical),Microbiology

Reference41 articles.

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3. Frieden Tom (2013). Antibiotic Resistance Threats in the United States 2013, CDC.

4. Office for National Statistics (2023, February 14). Deaths Involving Clostridium difficile, England and Wales 2012, Available online: http://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/bulletins/deathsinvolvingclostridiumdifficileenglandandwales/2013-08-22.

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