Clostridioides difficile phage biology and application

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. This review describes the current knowledge of C. difficile phage structure and replication with a focus on how this understanding can be applied to the development of novel therapies against C. difficile infections.

Automated summary

Clostridioides difficile, formerly known as Clostridium difficile, is the causative agent of C. difficile infections, which pose challenges in healthcare settings. Antibiotic-induced dysbiosis allows C. difficile colonization in the gut. Phage infection offers potential new treatment strategies against C. difficile infections.