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The advent of modern cryogenic electron microscopy (cryoEM) has revolutionized our understanding of these contractile injection systems, providing high-resolution insights into their mechanisms. We compare the structures of\n                    <jats:italic>C. difficile<\/jats:italic>\n                    phages and diffocins, highlighting their adaptations for penetrating the Gram-positive bacterial cell envelope \u2013 including the cell membrane, cell wall and proteinaceous surface layer. Diffocins, simpler in structure, utilize a combination of mechanical and enzymatic strategies, while some phages like \u03a6CD508 may rely on mechanical force alone. This review delves into the assembly and function of key components such as the contractile sheath, baseplate and receptor-binding proteins, offering a framework for engineering precision antimicrobials. We also present new experimental results, including refined cryoEM structures of the \u03a6CD508 pre- and post-contracted tail, a novel spontaneously contracted conformation and an X-ray crystal structure of a phage receptor-binding protein domain. This work underscores the potential of cryoEM in advancing our understanding of phage biology and its applications in developing targeted therapies against\n                    <jats:italic>C. difficile<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1107\/s2052252526005105","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T01:24:38Z","timestamp":1780449878000},"page":"324-342","update-policy":"https:\/\/doi.org\/10.1107\/cm_01","source":"Crossref","is-referenced-by-count":1,"title":["How cryoEM has advanced our understanding of bacteriophages and bacteriocins targeting\n                    <i>Clostridioides difficile<\/i>"],"prefix":"10.1107","volume":"13","author":[{"given":"Per A.","family":"Bullough","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05krs5044","id-type":"ROR","asserted-by":"publisher"}],"department":["Molecular Microbiology and Florey Institute of Infection, School of Biosciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason S.","family":"Wilson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05krs5044","id-type":"ROR","asserted-by":"publisher"}],"department":["Molecular Microbiology and Florey Institute of Infection, School of Biosciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7280-1048","authenticated-orcid":true,"given":"Hannah L.","family":"Berry","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05krs5044","id-type":"ROR","asserted-by":"publisher"}],"department":["Molecular Microbiology and Florey Institute of Infection, School of Biosciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8704-4828","authenticated-orcid":true,"given":"Robert P.","family":"Fagan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05krs5044","id-type":"ROR","asserted-by":"publisher"}],"department":["Molecular Microbiology and Florey Institute of Infection, School of Biosciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"329","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"rq5019_bb1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"rq5019_bb2","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1107\/S0907444909052925","volume":"66","author":"Adams","year":"2010","journal-title":"Acta Cryst. 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