Characterization of an endolysin targeting Clostridioides difficile that affects spore outgrowth.

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Mondal, Shakhinur Islam
Akter, Arzuba
Draper, Lorraine A.
Ross, R. Paul
Hill, Colin
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Clostridioides difficile 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, C. difficile infection. Therefore, there is an urgent need for novel therapeutics that are effective in preventing C. difficile 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 C. difficile phage, phiMMP01. The full-length CWH displayed lytic activity against selected C. difficile strains. However, removing the N-terminal cell wall binding domain, creating CWH351—656, resulted in increased and/or an expanded lytic spectrum of activity. C. difficile specificity was retained versus commensal clostridia and other bacterial species. As expected, the putative cell wall binding domain, CWH1—350, was completely inactive. We also observe the effect of CWH351—656 on preventing C. difficile spore outgrowth. Our results suggest that CWH351—656 has therapeutic potential as an antimicrobial agent against C. difficile infection.
Clostridioides difficile infection , Antibiotics , Antimicrobial agent , Antimicrobial resistance , Endolysin , Enteric pathogen
Mondal, S. I., Akter, A., Draper, L. A., Ross, R. P. and Hill, C. (2021) 'Characterization of an endolysin targeting Clostridioides difficile that affects spore outgrowth', International Journal of Molecular Sciences, 22(11), 5690 (14pp). doi: 10.3390/ijms22115690
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