The Evolutionary Adventures of Clostridioides difficile ribotype 017

Clostridioides difficile ribotype (RT) 017 ranks among the most successful C. difficile lineages globally. In the past three decades, it has caused outbreaks on at least four continents, more than other epidemic lineages. However, our understanding of the genomic basis for the spread of C. difficile RT 017 is limited, with a single study to date estimating the rapid global spread to have commenced in the 1990s. Here, we performed high-resolution core genome single nucleotide polymorphism (cgSNP) and Bayesian evolutionary analyses on an updated and more balanced dataset of 282 non-clonal C. difficile RT 017 genomes from strains isolated between 1981 and 2019 spanning six continents. These analyses place an estimated time of global spread between 1953 and 1983 and identified the acquisition of the ermB-positive transposon Tn6194 as a key factor behind this spread. This coincided with the introduction of clindamycin, a key inciter of C. difficile infection, into clinical practice in the 1960s. Based solely on the genomic data, 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 in 1860 (95% CI: 1622 – 1954). A focused study of 45 clinical C. difficile RT 017 genomes from a possible outbreak in a tertiary hospital in Thailand revealed that the population consisted of at least three different groups: two groups of multidrug-resistant (MDR) C. difficile RT 017 and a group of more ancient, non-MDR C. difficile RT 017. The significant genomic diversity within each MDR group suggests that though they were all isolated from hospitalised patients, there was likely an environmental reservoir of C. difficile RT 017 in the community that contributed to the spread of this pathogen.