Characterization of an Endolysin Targeting <i>Clostridioides difficile</i> That Affects Spore Outgrowth

Characterization of an Endolysin Targeting <i>Clostridioides difficile</i> That Affects Spore Outgrowth

<i>Clostridioides difficile</i> is a spore-forming enteric pathogen causing life-threatening diarrhoea and colitis. Microbial disruption caused by antibiotics has been linked with susceptibility to, and transmission and relapse of, <i>C. difficile</i> infection. Therefore, th...

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Bibliographic Details
Main Authors: Shakhinur Islam Mondal, Arzuba Akter, Lorraine A. Draper, R. Paul Ross, Colin Hill
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:International Journal of Molecular Sciences
Subjects:
<i>Clostridioides difficile</i> infection
endolysin
antimicrobial agent
antimicrobial resistance
enteric pathogen
antibiotics
Online Access:https://www.mdpi.com/1422-0067/22/11/5690
Description
Summary:<i>Clostridioides difficile</i> is a spore-forming enteric pathogen causing life-threatening diarrhoea and colitis. Microbial disruption caused by antibiotics has been linked with susceptibility to, and transmission and relapse of, <i>C. difficile</i> infection. Therefore, there is an urgent need for novel therapeutics that are effective in preventing <i>C. difficile</i> growth, spore germination, and outgrowth. In recent years bacteriophage-derived endolysins and their derivatives show promise as a novel class of antibacterial agents. In this study, we recombinantly expressed and characterized a cell wall hydrolase (CWH) lysin from <i>C. difficile</i> phage, phiMMP01. The full-length CWH displayed lytic activity against selected <i>C. difficile</i> strains. However, removing the N-terminal cell wall binding domain, creating CWH<sub>351—656</sub>, resulted in increased and/or an expanded lytic spectrum of activity. <i>C. difficile</i> specificity was retained versus commensal clostridia and other bacterial species. As expected, the putative cell wall binding domain, CWH<sub>1—350</sub>, was completely inactive. We also observe the effect of CWH<sub>351—656</sub> on preventing <i>C. difficile</i> spore outgrowth. Our results suggest that CWH<sub>351—656</sub> has therapeutic potential as an antimicrobial agent against <i>C. difficile</i> infection.
ISSN:1661-6596
1422-0067

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