Emergence and global spread of epidemic healthcare-associated Clostridium difficile

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 SenohTom Louie, Stephen Michell, Emma Butt, Sharon J. Peacock, Nicholas Brown, Tom Riley, Glen Songer, Mark Wilcox, Munir Pirmohamed, Ed Kuijper, Peter Hawkey, Brendan W. Wren, Gordon Dougan, Julian Parkhill, Trevor D. Lawley*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

498 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)109-113
Number of pages5
JournalNature Genetics
Issue number1
Publication statusPublished - Jan 2013

Bibliographical note

Funding Information:
We are grateful to members of the European Study Group of Clostridium difficile (ESGCD), a working group of ESCMID (European Society of Clinical Microbiology and Infectious Diseases), including F. Barbut, T. Eckmanns, M.L. Lambert, F. Fitzpatrick, C. Wiuff, H. Pituch, P. Reichert, A.F. Widmer, F. Allerberger, D.W. Notermans, M. Delmée, R. Frei, O. Lyytikäinen, A. Ingebretsen and I.R. Poxton. We thank the Wellcome Trust Sanger Institute sequencing and informatics teams. This project was funded by the Wellcome Trust (grants 098051 and 086418), a Medical Research Council New Investigator Research Grant (T.D.L.; grant 93614) and the Scottish Infection Research Network.

Funding Information:
We acknowledge funding from the National Institute for Health Research (NIHR) Biomedical Research Centre in Liverpool. Both F.M. and P.R. were supported by the Liverpool BRC (Biomedical Research Centre). M.P. is an NIHR Senior Investigator.


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