4.7 Review

Clostridioides difficile phage biology and application

Journal

FEMS MICROBIOLOGY REVIEWS
Volume 45, Issue 5, Pages -

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/femsre/fuab012

Keywords

Clostridioides difficile; C. difficile infection; bacteriophage; phage therapy

Categories

Funding

  1. National Institutes of Health [R01-AI132711]
  2. Natural Sciences and Engineering Research Council of Canada [NSERC RGPIN-2020-05776]

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Clostridioides difficile, previously known as Clostridium difficile, is the causative agent of CDI. Antibiotics-induced dysbiosis of the microbiota is the primary factor allowing C. difficile to colonize the gut and cause diseases. Phages infecting C. difficile could offer new treatment strategies and insights into its biology.
Clostridium difficile, now reclassified as Clostridioides difficile, is the causative agent of C. difficile infections (CDI). CDI is particularly challenging in healthcare settings because highly resistant spores of the bacterium can persist in the environment, making it difficult to curb outbreaks. Dysbiosis of the microbiota caused by the use of antibiotics is the primary factor that allows C. difficile to colonize the gut and cause diarrhea and colitis. For this reason, antibiotics targeting C. difficile can be ineffective at preventing recurrent episodes because they exacerbate and prolong dysbiosis. The emergence of antibiotic resistance in C. difficile also presents a significant threat. The diverse array of bacteriophages (phages) that infect C. difficile could offer new treatment strategies and greater insight into the biology of the pathogen. In this review, we summarize the current knowledge regarding C. difficile phages and discuss what is understood about their lifestyles and genomics. Then, we examine how phage infection modifies bacterial gene expression and pathogenicity. Finally, we discuss the potential clinical applications of C. difficile phages such as whole phage therapy and phage-derived products, and we highlight the most promising strategies for further development.

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