{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:05:56Z","timestamp":1790136356124,"version":"4.0.1"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>Clostridioides difficile<\/jats:italic> is a significant cause of healthcare-associated infections, with rising antimicrobial resistance complicating treatment. This study offers a genomic analysis of <jats:italic>C. difficile<\/jats:italic>, focusing on sequence types (STs), global distribution, antibiotic resistance genes, and virulence factors in its chromosomal and plasmid DNA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 19,711 <jats:italic>C. difficile<\/jats:italic> genomes were retrieved from GenBank. Prokka was used for genome annotation, and multi-locus sequence typing (MLST) identified STs. Pan-genome analysis with Roary identified core and accessory genes. Antibiotic resistance genes, virulence factors, and toxins were detected using the CARD and VFDB databases, and the ABRicate software. Statistical analyses and visualizations were performed in R.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 366 identified STs, ST1 (1,326 isolates), ST2 (1,141), ST11 (893), and ST42 (763) were predominant. Trends of genome streamlining included reductions in chromosomal length, gene count, protein-coding genes, and pseudogenes. Common antibiotic resistance genes\u2014<jats:italic>cdeA<\/jats:italic> (99.46%), <jats:italic>cplR<\/jats:italic> (99.63%), and <jats:italic>nimB<\/jats:italic> (99.67%)\u2014were nearly ubiquitous. Rare resistance genes like <jats:italic>blaCTX-M-2<\/jats:italic>, <jats:italic>cfxA3<\/jats:italic>, and <jats:italic>blaZ<\/jats:italic> appeared in only 0.005% of genomes. Vancomycin susceptibility-reducing <jats:italic>vanG<\/jats:italic> cluster genes were detected at low frequencies. Virulence factors showed variability, with highly prevalent genes such as <jats:italic>zmp1<\/jats:italic> (99.62%), <jats:italic>groEL<\/jats:italic> (99.60%), and <jats:italic>rpoB\/rpoB2<\/jats:italic> (99.60%). Moderately distributed genes included <jats:italic>cwp66<\/jats:italic> (54.61%) and <jats:italic>slpA<\/jats:italic> (79.02%). Toxin genes <jats:italic>tcdE<\/jats:italic> (91.26%), <jats:italic>tcdC<\/jats:italic> (89.67%), and <jats:italic>tcdB<\/jats:italic> (89.06%) were widespread, while binary toxin genes <jats:italic>cdtA<\/jats:italic> (26.19%) and <jats:italic>cdtB<\/jats:italic> (26.26%) were less common. Toxin gene prevalence, particularly <jats:italic>tcdA<\/jats:italic> and <jats:italic>tcdB<\/jats:italic>, showed a gradual decline over time, with sharper reductions for <jats:italic>cdtA<\/jats:italic> and <jats:italic>cdtB<\/jats:italic>. Gene presence patterns (GPP-1) for resistance, virulence, and toxin genes were primarily linked to ST2, ST42, and ST8.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study highlights <jats:italic>C. difficile<\/jats:italic>\u2019s adaptability and genetic diversity. The decline in toxin genes reflects fewer toxigenic isolates, but the bacterium\u2019s increasing preserved resistance factors and virulence genes enable its rapid evolution. ST2, ST42, and ST8 dominate globally, emphasizing the need for ongoing monitoring.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2024.1493225","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T06:13:03Z","timestamp":1736921583000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Global insights into the genome dynamics of Clostridioides difficile associated with antimicrobial resistance, virulence, and genomic adaptations among clonal lineages"],"prefix":"10.3389","volume":"14","author":[{"given":"Mohammad","family":"Sholeh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoumeh","family":"Beig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebrahim","family":"Kouhsari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahdi","family":"Rohani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Katouli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzad","family":"Badmasti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1752","DOI":"10.3390\/microorganisms11071752","article-title":"Update on commonly used molecular typing methods for clostridioides difficile","volume":"11","author":"Abad-Fau","year":"2023","journal-title":"Microorganisms"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.2147\/CIA.S149089","article-title":"Clostridium difficile infection in the elderly: an update on management","volume":"12","author":"Asempa","year":"2017","journal-title":"Clin. 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