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dc.contributor.authorFrentrup, Martinique
dc.contributor.authorZhou, Zhemin
dc.contributor.authorSteglich, Matthias
dc.contributor.authorMeier-Kolthoff, Jan P
dc.contributor.authorGöker, Markus
dc.contributor.authorRiedel, Thomas
dc.contributor.authorBunk, Boyke
dc.contributor.authorSpröer, Cathrin
dc.contributor.authorOvermann, Jörg
dc.contributor.authorBlaschitz, Marion
dc.contributor.authorIndra, Alexander
dc.contributor.authorvon Müller, Lutz
dc.contributor.authorKohl, Thomas A
dc.contributor.authorNiemann, Stefan
dc.contributor.authorSeyboldt, Christian
dc.contributor.authorKlawonn, Frank
dc.contributor.authorKumar, Nitin
dc.contributor.authorLawley, Trevor D
dc.contributor.authorGarcía-Fernández, Sergio
dc.contributor.authorCantón, Rafael
dc.contributor.authorDel Campo, Rosa
dc.contributor.authorZimmermann, Ortrud
dc.contributor.authorGroß, Uwe
dc.contributor.authorAchtman, Mark
dc.contributor.authorNübel, Ulrich
dc.identifier.citationMicrob Genom. 2020 Aug;6(8):mgen000410. doi: 10.1099/mgen.0.000410. Epub 2020 Jul 29.en_US
dc.description.abstractClostridioides difficile is the primary infectious cause of antibiotic-associated diarrhea. Local transmissions and international outbreaks of this pathogen have been previously elucidated by bacterial whole-genome sequencing, but comparative genomic analyses at the global scale were hampered by the lack of specific bioinformatic tools. Here we introduce a publicly accessible database within EnteroBase ( that automatically retrieves and assembles C. difficile short-reads from the public domain, and calls alleles for core-genome multilocus sequence typing (cgMLST). We demonstrate that comparable levels of resolution and precision are attained by EnteroBase cgMLST and single-nucleotide polymorphism analysis. EnteroBase currently contains 18 254 quality-controlled C. difficile genomes, which have been assigned to hierarchical sets of single-linkage clusters by cgMLST distances. This hierarchical clustering is used to identify and name populations of C. difficile at all epidemiological levels, from recent transmission chains through to epidemic and endemic strains. Moreover, it puts newly collected isolates into phylogenetic and epidemiological context by identifying related strains among all previously published genome data. For example, HC2 clusters (i.e. chains of genomes with pairwise distances of up to two cgMLST alleles) were statistically associated with specific hospitals (P<10-4) or single wards (P=0.01) within hospitals, indicating they represented local transmission clusters. We also detected several HC2 clusters spanning more than one hospital that by retrospective epidemiological analysis were confirmed to be associated with inter-hospital patient transfers. In contrast, clustering at level HC150 correlated with k-mer-based classification and was largely compatible with PCR ribotyping, thus enabling comparisons to earlier surveillance data. EnteroBase enables contextual interpretation of a growing collection of assembled, quality-controlled C. difficile genome sequences and their associated metadata. Hierarchical clustering rapidly identifies database entries that are related at multiple levels of genetic distance, facilitating communication among researchers, clinicians and public-health officials who are combatting disease caused by C. difficile.en_US
dc.publisherMicrobiology Societyen_US
dc.relationinfo:eu-repo/grantAgreement/EC/ H2020/643476en_US
dc.rightsAttribution 4.0 International*
dc.subjectClostridioides (Clostridium) difficileen_US
dc.subjectgenomic population structureen_US
dc.subjecthierarchical clusteringen_US
dc.subjectnosocomial infectionen_US
dc.titleA publicly accessible database for genome sequences supports tracing of transmission chains and epidemics.en_US
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalMicrobial genomicsen_US
dc.source.journaltitleMicrobial genomics
dc.source.countryUnited Kingdom
dc.source.countryUnited Kingdom

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