title: Emergence and global spread of epidemic healthcare-associated Clostridium difficile.
abstract: 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.
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.forename: Fabio
authors.initials: F
authors.lastname: Miyajima
authors.forename: Paul
authors.initials: P
authors.lastname: Roberts
authors.forename: Louise
authors.initials: L
authors.lastname: Ellison
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Pickard
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Martin
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Connor
authors.forename: Simon R
authors.initials: SR
authors.lastname: Harris
authors.forename: Derek
authors.initials: D
authors.lastname: Fairley
authors.forename: Kathleen B
authors.initials: KB
authors.lastname: Bamford
authors.forename: Stephanie
authors.initials: S
authors.lastname: D'Arc
authors.forename: Jon
authors.initials: J
authors.lastname: Brazier
authors.forename: Derek
authors.initials: D
authors.lastname: Brown
authors.forename: John E
authors.initials: JE
authors.lastname: Coia
authors.forename: Gill
authors.initials: G
authors.lastname: Douce
authors.forename: Dale
authors.initials: D
authors.lastname: Gerding
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Tse Hsien
authors.initials: TH
authors.lastname: Koh
authors.forename: Haru
authors.initials: H
authors.lastname: Kato
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Senoh
authors.forename: Tom
authors.initials: T
authors.lastname: Louie
authors.forename: Stephen
authors.initials: S
authors.lastname: Michell
authors.forename: Emma
authors.initials: E
authors.lastname: Butt
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Peacock
authors.forename: Nick M
authors.initials: NM
authors.lastname: Brown
authors.forename: Tom
authors.initials: T
authors.lastname: Riley
authors.forename: Glen
authors.initials: G
authors.lastname: Songer
authors.forename: Mark
authors.initials: M
authors.lastname: Wilcox
authors.forename: Munir
authors.initials: M
authors.lastname: Pirmohamed
authors.forename: Ed
authors.initials: E
authors.lastname: Kuijper
authors.forename: Peter
authors.initials: P
authors.lastname: Hawkey
authors.forename: Brendan W
authors.initials: BW
authors.lastname: Wren
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.forename: Trevor D
authors.initials: TD
authors.lastname: Lawley
mesh_terms: D016360:Clostridioides difficile / Q000145:classification / Q000235:genetics*; D003967:Diarrhea / Q000453:epidemiology*; D004761:Enterocolitis, Pseudomembranous / Q000453:epidemiology*; D058872:Epidemics; D016680:Genome, Bacterial; D005838:Genotype; D006801:Humans; D010802:Phylogeny; D058974:Phylogeography; D020641:Polymorphism, Single Nucleotide