{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T18:56:22Z","timestamp":1767984982155,"version":"3.49.0"},"reference-count":33,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T00:00:00Z","timestamp":1608508800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009228","name":"Research Committee of Region \u00d6rebro County","doi-asserted-by":"publisher","award":["OLL-674241"],"award-info":[{"award-number":["OLL-674241"]}],"id":[{"id":"10.13039\/501100009228","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>A zoonotic association has been suggested for several PCR ribotypes (RTs) of <jats:italic>Clostridioides difficile<\/jats:italic>. In central parts of Sweden, RT046 was found dominant in neonatal pigs at the same time as a RT046 hospital <jats:italic>C<\/jats:italic>. <jats:italic>difficile<\/jats:italic> infection (CDI) outbreak occurred in the southern parts of the country.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>To detect possible transmission of RT046 between pig farms and human CDI cases in Sweden and investigate the diversity of RT046 in the pig population using whole genome sequencing (WGS).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>WGS was performed on 47 <jats:italic>C<\/jats:italic>. <jats:italic>difficile<\/jats:italic> isolates from pigs (n = 22), the farm environment (n = 7) and human cases of CDI (n = 18). Two different core genome multilocus sequencing typing (cgMLST) schemes were used together with a single nucleotide polymorphisms (SNP) analysis and the results were related to time and location of isolation of the isolates.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>The pig isolates were closely related (\u22646 cgMLST alleles differing in both cgMLST schemes) and conserved over time and were clearly separated from isolates from the human hospital outbreak (\u226576 and \u226590 cgMLST alleles differing in the two cgMLST schemes). However, two human isolates were closely related to the pig isolates, suggesting possible transmission. The SNP analysis was not more discriminate than cgMLST.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>No general pattern suggesting zoonotic transmission was apparent between pigs and humans, although contrasting results from two isolates still make transmission possible. Our results support the need for high resolution WGS typing when investigating hospital and environmental transmission of <jats:italic>C<\/jats:italic>. <jats:italic>difficile<\/jats:italic>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0244227","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T18:43:23Z","timestamp":1608576203000},"page":"e0244227","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":27,"title":["Whole genome sequencing of Clostridioides difficile PCR ribotype 046 suggests transmission between pigs and 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and economic burden of Clostridium difficile infection in Europe: a systematic review of healthcare-facility-acquired infection","volume":"81","author":"PN Wiegand","year":"2012","journal-title":"Journal of Hospital Infection"},{"issue":"1","key":"pone.0244227.ref002","doi-asserted-by":"crossref","first-page":"010407","DOI":"10.7189\/jogh.09.010407","article-title":"Global burden of Clostridium difficile infections: a systematic review and meta-analysis","volume":"9","author":"E Balsells","year":"2019","journal-title":"J Glob Health"},{"issue":"Suppl 6","key":"pone.0244227.ref003","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1469-0691.2006.01580.x","article-title":"Emergence of Clostridium difficile-associated disease in North America and Europe","volume":"12","author":"EJ Kuijper","year":"2006","journal-title":"Clin Microbiol Infect"},{"issue":"9","key":"pone.0244227.ref004","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1056\/NEJMoa1408913","article-title":"Burden of Clostridium difficile Infection in the United States","volume":"372","author":"FC Lessa","year":"2015","journal-title":"New England Journal of Medicine"},{"issue":"4","key":"pone.0244227.ref005","doi-asserted-by":"crossref","first-page":"20381","DOI":"10.2807\/ese.18.04.20381-en","article-title":"Current application and future perspectives of molecular typing methods to study Clostridium difficile infections","volume":"18","author":"CW Knetsch","year":"2013","journal-title":"Euro Surveill"},{"issue":"3","key":"pone.0244227.ref006","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1093\/jpids\/piv020","article-title":"Comparison of Whole-Genome Sequencing and Molecular-Epidemiological Techniques for Clostridium difficile Strain Typing","volume":"5","author":"SR Dominguez","year":"2016","journal-title":"J Pediatric Infect Dis Soc."},{"issue":"13","key":"pone.0244227.ref007","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1056\/NEJMoa1216064","article-title":"Diverse sources of C. difficile infection identified on whole-genome sequencing","volume":"369","author":"DW Eyre","year":"2013","journal-title":"N Engl J Med"},{"issue":"8","key":"pone.0244227.ref008","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1111\/j.1469-0691.2011.03651.x","article-title":"Clostridium difficile in Dutch animals: their presence, characteristics and similarities with human isolates","volume":"18","author":"MG Koene","year":"2012","journal-title":"Clin Microbiol Infect"},{"issue":"4","key":"pone.0244227.ref009","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1177\/104063870201400402","article-title":"A survey of agents associated with neonatal diarrhea in Iowa swine including Clostridium difficile and porcine reproductive and respiratory syndrome virus","volume":"14","author":"M Yaeger","year":"2002","journal-title":"J Vet Diagn Invest"},{"key":"pone.0244227.ref010","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.3389\/fmicb.2016.02138","article-title":"Genome Analysis of Clostridium difficile PCR Ribotype 014 Lineage in Australian Pigs and Humans Reveals a Diverse Genetic Repertoire and Signatures of Long-Range Interspecies Transmission","volume":"7:","author":"DR Knight","year":"2017","journal-title":"Frontiers in microbiology"},{"issue":"45","key":"pone.0244227.ref011","doi-asserted-by":"crossref","first-page":"20954","DOI":"10.2807\/1560-7917.ES2014.19.45.20954","article-title":"Whole genome sequencing reveals potential spread of Clostridium difficile between humans and farm animals in the Netherlands, 2002 to 2011","volume":"19","author":"CW Knetsch","year":"2014","journal-title":"Euro Surveill"},{"issue":"3","key":"pone.0244227.ref012","doi-asserted-by":"crossref","DOI":"10.1128\/JCM.01384-17","article-title":"Zoonotic Transfer of Clostridium difficile Harboring Antimicrobial Resistance between Farm Animals and Humans","volume":"56","author":"CW Knetsch","year":"2018","journal-title":"J Clin Microbiol"},{"issue":"8","key":"pone.0244227.ref013","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1007\/s10096-013-1845-5","article-title":"Emergence of Clostridium difficile infection in tuberculosis patients due to a highly rifampicin-resistant PCR ribotype 046 clone in Poland","volume":"32","author":"P Obuch-Woszczatynski","year":"2013","journal-title":"Eur J Clin Microbiol Infect Dis"},{"issue":"5","key":"pone.0244227.ref014","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1017\/S0950268815002459","article-title":"Predominance of Clostridium difficile ribotypes 012, 027 and 046 in a university hospital in Chile, 2012","volume":"144","author":"A Plaza-Garrido","year":"2016","journal-title":"Epidemiol Infect"},{"issue":"9","key":"pone.0244227.ref015","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.3201\/eid2409.171658","article-title":"National Surveillance for Clostridioides difficile Infection, Sweden, 2009\u20132016","volume":"24","author":"K Rizzardi","year":"2018","journal-title":"Emerging infectious diseases"},{"issue":"1","key":"pone.0244227.ref016","doi-asserted-by":"crossref","first-page":"O2","DOI":"10.1111\/1469-0691.12296","article-title":"Clostridium difficile PCR ribotype 046 is common among neonatal pigs and humans in Sweden","volume":"20","author":"T Noren","year":"2014","journal-title":"Clin Microbiol Infect"},{"key":"pone.0244227.ref017","article-title":"Using the Velvet de novo assembler for short-read sequencing technologies","author":"DR Zerbino","year":"2010","journal-title":"Curr Protoc Bioinformatics"},{"issue":"5","key":"pone.0244227.ref018","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1089\/cmb.2012.0021","article-title":"SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing","volume":"19","author":"A Bankevich","year":"2012","journal-title":"J Comput Biol"},{"key":"pone.0244227.ref019","first-page":"56","article-title":"Defining and Evaluating a Core Genome Multilocus Sequence Typing Scheme for Genome-Wide Typing of Clostridium difficile","author":"S Bletz","year":"2018","journal-title":"J Clin Microbiol"},{"issue":"3","key":"pone.0244227.ref020","doi-asserted-by":"crossref","first-page":"e0151964","DOI":"10.1371\/journal.pone.0151964","article-title":"Molecular Characterization of Clostridium difficile Isolates from Human Subjects and the Environment","volume":"11","author":"T-T Tian","year":"2016","journal-title":"PLoS One."},{"issue":"14","key":"pone.0244227.ref021","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"H Li","year":"2009","journal-title":"Bioinformatics"},{"key":"pone.0244227.ref022","unstructured":"Li H. Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. arXiv preprint arXiv:13033997. 2013."},{"key":"pone.0244227.ref023","unstructured":"Garrison E, Marth G. Haplotype-based variant detection from short-read sequencing. arXiv preprint arXiv:12073907. 2012."},{"issue":"4","key":"pone.0244227.ref024","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.cmi.2017.12.016","article-title":"Whole genome sequencing options for bacterial strain typing and epidemiologic analysis based on single nucleotide polymorphism versus gene-by-gene-based approaches","volume":"24","author":"AC Schurch","year":"2018","journal-title":"Clin Microbiol Infect"},{"issue":"3","key":"pone.0244227.ref025","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1128\/JCM.01296-16","article-title":"Comparative Genome Analysis and Global Phylogeny of the Toxin Variant Clostridium difficile PCR Ribotype 017 Reveals the Evolution of Two Independent Sublineages","volume":"55","author":"MD Cairns","year":"2017","journal-title":"J Clin Microbiol"},{"issue":"3","key":"pone.0244227.ref026","article-title":"A pilot study of rapid benchtop sequencing of Staphylococcus aureus and Clostridium difficile for outbreak detection and surveillance","volume":"2","author":"DW Eyre","year":"2012","journal-title":"BMJ Open"},{"issue":"4","key":"pone.0244227.ref027","doi-asserted-by":"crossref","DOI":"10.2807\/1560-7917.ES.2019.24.4.1800186","article-title":"Whole genome sequencing of Salmonella Chester reveals geographically distinct clusters, Norway, 2000 to 2016","volume":"24","author":"L Siira","year":"2019","journal-title":"Euro Surveill"},{"issue":"12","key":"pone.0244227.ref028","doi-asserted-by":"crossref","first-page":"3788","DOI":"10.1128\/JCM.01946-15","article-title":"Core Genome Multilocus Sequence Typing Scheme for High-Resolution Typing of Enterococcus faecium","volume":"53","author":"M de Been","year":"2015","journal-title":"J Clin Microbiol"},{"key":"pone.0244227.ref029","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijfoodmicro.2018.02.023","article-title":"Comparative analysis of core genome MLST and SNP typing within a European Salmonella serovar Enteritidis outbreak","volume":"274","author":"ME Pearce","year":"2018","journal-title":"Int J Food Microbiol"},{"issue":"1","key":"pone.0244227.ref030","first-page":"e01037","article-title":"Hash-Based Core Genome Multilocus Sequence Typing for Clostridium difficile","volume":"58","author":"DW Eyre","year":"2019","journal-title":"J Clin Microbiol"},{"issue":"12","key":"pone.0244227.ref031","doi-asserted-by":"crossref","first-page":"R118","DOI":"10.1186\/gb-2012-13-12-r118","article-title":"Microevolutionary analysis of Clostridium difficile genomes to investigate transmission","volume":"13","author":"X Didelot","year":"2012","journal-title":"Genome biology"},{"issue":"3","key":"pone.0244227.ref032","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1128\/CMR.00127-14","article-title":"Diversity and Evolution in the Genome of Clostridium difficile","volume":"28","author":"DR Knight","year":"2015","journal-title":"Clin Microbiol Rev"},{"issue":"1","key":"pone.0244227.ref033","doi-asserted-by":"crossref","first-page":"11293","DOI":"10.1038\/s41598-019-47688-2","article-title":"Integrated genomic epidemiology and phenotypic profiling of Clostridium difficile across intra-hospital and community populations in Colombia","volume":"9","author":"M Munoz","year":"2019","journal-title":"Sci Rep"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0244227","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T18:43:58Z","timestamp":1608576238000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0244227"}},"subtitle":[],"editor":[{"given":"Yung-Fu","family":"Chang","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2020,12,21]]},"references-count":33,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0244227","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,21]]}}}