Emergence and global spread of epidemic healthcare-associated Clostridium difficile

• DOI: 10.1038/ng.2478
• Publication Date: 2012-12-09T20:07:21Z
• Authors: Miao He; Fabio Miyajima; Paul Roberts; Louise Ellison; Derek J Pickard; Melissa J Martin; Thomas R Connor; Simon R Harris; Derek Fairley; Kathleen B Bamford; Stephanie D'Arc; Jon Brazier; Derek Brown; John E Coia; Gill Douce; Dale Gerding; Hee Jung Kim; Tse Hsien Koh; Haru Kato; Mitsutoshi Senoh; Tom Louie; Stephen Michell; Emma Butt; Sharon J Peacock; Nick M Brown; Tom Riley; Glen Songer; Mark Wilcox; Munir Pirmohamed; Ed Kuijper; Peter Hawkey; Brendan W Wren; Gordon Dougan; Julian Parkhill; Trevor D Lawley
• Keywords: Diarrhea; 0301 basic medicine; 570; Genotype; 612; Polymorphism, Single Nucleotide; Article; Clostridium difficile/classification; 03 medical and health sciences; Diarrhea/epidemiology*; 616; Humans; Polymorphism; Epidemics; Enterocolitis, Pseudomembranous; Phylogeny; 0303 health sciences; Clostridium difficile/genetics*; Genome; Enterocolitis; Clostridioides difficile; Bacterial; population genetics; Single Nucleotide; Pseudomembranous/epidemiology*; clostridium difficile; 3. Good health; phylogenetics; Phylogeography; Genome, Bacterial

Epidemic C. difficile (027/BI/NAP1) has rapidly emerged in the past decade as the leading cause of antibiotic-associated diarrhea worldwide. However, the key events in evolutionary history leading to its emergence and the subsequent patterns of global spread remain unknown. Here, we define the global population structure of C. difficile 027/BI/NAP1 using whole-genome sequencing and phylogenetic analysis. We show that two distinct epidemic lineages, FQR1 and FQR2, not one as previously thought, emerged in North America within a relatively short period after acquiring the same fluoroquinolone resistance-conferring mutation and a highly related conjugative transposon. The two epidemic lineages showed distinct patterns of global spread, and the FQR2 lineage spread more widely, leading to healthcare-associated outbreaks in the UK, continental Europe and Australia. Our analysis identifies key genetic changes linked to the rapid transcontinental dissemination of epidemic C. difficile 027/BI/NAP1 and highlights the routes by which it spreads through the global healthcare system.