Evolutionary and genomic insights into Clostridioides difficile sequence type 11: a diverse, zoonotic and antimicrobial resistant lineage of global One Health importance. mBio 10:e00446-19. https:// doi.org/10.1128/mBio.00446-19.. Clostridium difficile sequence type 11

Clostridioides (Clostridium) difficile sequence type (ST) 11 is well established in production animal populations worldwide and contributes considerably to the global burden of C. difficile infection (CDI) in humans. Increasing evidence of shared ancestry and genetic overlap of PCR ribotype (RT) 078, the most common ST11 sub-lineage, between human and animal populations suggests that CDI may be a zoonosis. We performed whole-genome sequencing (WGS) on a collection of 207 ST11 and closely related ST258 isolates of human and veterinary/environmental origin, comprising 16 RTs collected from Australia, Asia, Europe and North America. Core genome single nucleotide variant (SNV) analysis identified multiple intra-species and inter-species clonal groups (isolates separated by ≤ 2 core genome SNVs) in all the major RT sub-lineages; 078, 126, 127, 033 and 288. Clonal groups comprised isolates spread across different states, countries and continents, indicative of reciprocal long-range dissemination and possible zoonotic/ anthroponotic transmission. Antimicrobial resistance genotypes and phenotypes varied across host species, geographic regions and RTs, and included macrolide/lincosamide resistance (Tn6194; ermB), tetracycline resistance (Tn6190; tetM and Tn6164; tet44), fluoroquinolone resistance (gyrA/B mutations) as well as numerous aminoglycoside resistance cassettes. The population was defined by a large ‘open’ pan-genome (10378 genes), a remarkably small core genome of 2058 genes (only 19.8% of the gene pool) and an accessory genome containing a large and diverse collection of important prophages of the Siphoviridae and Myoviridae. This study provides novel insights into strain relatedness and genetic variability of C. difficile ST11, a lineage of global One Health importance.