Phylogenomic analysis of Clostridiodes difficile ribotype 106 strains reveals novel genetic islands and emergent phenotypes

Background: Clostridioides difficile RT106 has emerged as a dominant molecular type in the USA in recent years, but the underlying factors contributing to its predominance remain undefined. As part of our ongoing C. difficile infection (CDI) surveillance in Arizona, we monitored RT106 frequency and characterized the genomic and phenotypic properties of the recovered isolates. Results: From 2015-2018, RT106 was the second-most prevalent molecular type isolated from CDI patients in our surveillance. A representative RT106 strain displayed robust virulence and 100% lethality in the hamster model of acute CDI. We identified a unique 46 KB genomic island (GI1) in all RT106 strains, including those in public databases. GI1 was not found in its entirety in any other C. difficile clade, or indeed in any other microbial genome; however, smaller segments were detected in select Enterococcus faecium strains. Molecular clock analyses suggest that GI1 was horizontally acquired and sequentially assembled over time. Consistent with the presence of genes encoding homologs of VanZ and a SrtB-anchored collagen-binding adhesin in GI1, all tested RT106 strains had increased teicoplanin resistance and a majority displayed collagen-dependent biofilm formation. Two additional genomic islands (GI2 and GI3) were also present in a subset of RT106 strains. All three islands have features of mobile genetic elements and encode several putative virulence factors. Conclusions: Consistent with the known genetic plasticity of C. difficile, strains belonging to the RT106 clade harbor unique genetic islands. Correspondingly, emergent phenotypic properties may contribute to the relatively rapid shifts of strain distribution in patient populations.