Comparative genomics reveals diversity and taxonomic relationships among <i>Clostridioides difficile</i> phages

<i>Clostridioides difficile</i> is a significant healthcare concern due to its role in causing severe infections and its increasing resistance to antibiotics. Phages present a promising alternative to antibiotics for combating bacterial pathogens, including <i>C. difficile</i>. Our study is the first comprehensive comparative genomic analysis of <i>C. difficile</i> phage genomes. We analyzed all available <i>C. difficile</i> phage genomes and clustered them into genetically distinct groups based on protein sharing. We also propose major taxonomic revisions to facilitate the accurate classification of <i>C. difficile</i> phages. Additionally, we investigated the lytic module of these phages, revealing diverse endolysin organizations and strong purifying selection acting on the catalytic and cell wall binding domains. Our findings contribute valuable insights into the biology of <i>C. difficile</i> phages and provide a framework that can aid in the classification and genomic analysis of newly isolated <i>C. difficile</i> phages in the future.