Global evolutionary dynamics and resistome analysis of Clostridioides difficile ribotype 017

AbstractClostridioides difficile PCR ribotype (RT) 017 ranks among the most successful strains of C. difficile in the world. In the past three decades, it has caused outbreaks on four continents, more than other “epidemic” strains, however, our understanding of the genomic epidemiology underpinning the spread of C. difficile RT 017 is limited. Here, we performed high-resolution phylogenomic and Bayesian evolutionary analyses on an updated and more representative dataset of 282 non-clonal C. difficile RT 017 isolates collected worldwide between 1981 and 2019. These analyses place an estimated time of global dissemination between 1953 and 1983 and identified the acquisition of the ermB-positive transposon Tn6194 as a key factor behind global emergence. This coincided with the introduction of clindamycin, a key inciter of C. difficile infection, into clinical practice in the 1960s. Based on the genomic data alone, the origin of C. difficile RT 017 could not be determined, however, geographical data and records of population movement suggest that C. difficile RT 017 had been moving between Asia and Europe since the Middle Ages and was later transported to North America around 1860 (95% CI: 1622 – 1954). A focused epidemiological study of 45 clinical C. difficile RT 017 genomes from a cluster in a tertiary hospital in Thailand revealed that the population consisted of two groups of multidrug-resistant (MDR) C. difficile RT 017 and a group of early, non-MDR C. difficile RT 017. The significant genomic diversity within each MDR group suggests that although they were all isolated from hospitalised patients, there was likely a reservoir of C. difficile RT 017 in the community that contributed to the spread of this pathogen.Impact statementThis study utilises genomic sequence data from 282 non-clonal C. difficile ribotype (RT) 017 isolates collected from around the world to delineate the origin and spread of this epidemic lineage, as well as explore possible factors that have driven its success. It also reports a focused epidemiological investigation of a cluster of C. difficile RT 017 in a tertiary hospital in Thailand to identify possible sources of transmission in this specific setting.Data summaryAll new WGS data generated in this study has been submitted to the European Nucleotide Archive under the BioProject PRJEB44406 (sample accession ERS6268756 – ERS6268798). The complete genome of C. difficile MAR286 was submitted to GenBank under BioProject PRJNA679085 (accession CP072118). Details of all genomes included in the final analyses are available in the Supplementary Document, available at 10.6084/m9.figshare.14544792.