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 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

doi:10.1038/ng.2478

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, 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

586 Citations (Scopus)

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.

Original language	English
Pages (from-to)	109-113
Number of pages	5
Journal	Nature Genetics
Volume	45
Issue number	1
Early online date	09 Dec 2012
DOIs	https://doi.org/10.1038/ng.2478
Publication status	Published - Jan 2013
Externally published	Yes

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.

ASJC Scopus subject areas

Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ng.2478Licence: Unspecified

Cite this

He, M., Miyajima, F., Roberts, P., Ellison, L., Pickard, D. J., Martin, M. J., Connor, T. R., Harris, S. R., Fairley, D., Bamford, K. B., D'Arc, S., Brazier, J., Brown, D., Coia, J. E., Douce, G., Gerding, D., Kim, H. J., Koh, T. H., Kato, H., ... Lawley, T. D. (2013). Emergence and global spread of epidemic healthcare-associated Clostridium difficile. Nature Genetics, 45(1), 109-113. https://doi.org/10.1038/ng.2478

@article{edad68fd9e0747fd801b09146c6f5927,

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.",

author = "Miao He and Fabio Miyajima and Paul Roberts and Louise Ellison and Pickard, {Derek J.} and Martin, {Melissa J.} and Connor, {Thomas R.} and Harris, {Simon R.} and Derek Fairley and Bamford, {Kathleen B.} and Stephanie D'Arc and Jon Brazier and Derek Brown and Coia, {John E.} and Gill Douce and Dale Gerding and Kim, {Hee Jung} and Koh, {Tse Hsien} and Haru Kato and Mitsutoshi Senoh and Tom Louie and Stephen Michell and Emma Butt and Peacock, {Sharon J.} and Brown, {Nick M.} and Tom Riley and Glen Songer and Mark Wilcox and Munir Pirmohamed and Ed Kuijper and Peter Hawkey and Wren, {Brendan W.} and Gordon Dougan and Julian Parkhill and Lawley, {Trevor D.}",

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. Delm{\'e}e, R. Frei, O. Lyytik{\"a}inen, 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.",

year = "2013",

month = jan,

doi = "10.1038/ng.2478",

language = "English",

volume = "45",

pages = "109--113",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "1",

}

He, M, Miyajima, F, Roberts, P, Ellison, L, Pickard, DJ, Martin, MJ, Connor, TR, Harris, SR, Fairley, D, Bamford, KB, D'Arc, S, Brazier, J, Brown, D, Coia, JE, Douce, G, Gerding, D, Kim, HJ, Koh, TH, Kato, H, Senoh, M, Louie, T, Michell, S, Butt, E, Peacock, SJ, Brown, NM, Riley, T, Songer, G, Wilcox, M, Pirmohamed, M, Kuijper, E, Hawkey, P, Wren, BW, Dougan, G, Parkhill, J & Lawley, TD 2013, 'Emergence and global spread of epidemic healthcare-associated Clostridium difficile', Nature Genetics, vol. 45, no. 1, pp. 109-113. https://doi.org/10.1038/ng.2478

TY - JOUR

T1 - Emergence and global spread of epidemic healthcare-associated Clostridium difficile

AU - He, Miao

AU - Miyajima, Fabio

AU - Roberts, Paul

AU - Ellison, Louise

AU - Pickard, Derek J.

AU - Martin, Melissa J.

AU - Connor, Thomas R.

AU - Harris, Simon R.

AU - Fairley, Derek

AU - Bamford, Kathleen B.

AU - D'Arc, Stephanie

AU - Brazier, Jon

AU - Brown, Derek

AU - Coia, John E.

AU - Douce, Gill

AU - Gerding, Dale

AU - Kim, Hee Jung

AU - Koh, Tse Hsien

AU - Kato, Haru

AU - Senoh, Mitsutoshi

AU - Louie, Tom

AU - Michell, Stephen

AU - Butt, Emma

AU - Peacock, Sharon J.

AU - Brown, Nick M.

AU - Riley, Tom

AU - Songer, Glen

AU - Wilcox, Mark

AU - Pirmohamed, Munir

AU - Kuijper, Ed

AU - Hawkey, Peter

AU - Wren, Brendan W.

AU - Dougan, Gordon

AU - Parkhill, Julian

AU - Lawley, Trevor D.

N1 - 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.

PY - 2013/1

Y1 - 2013/1

N2 - 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.

AB - 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.

U2 - 10.1038/ng.2478

DO - 10.1038/ng.2478

M3 - Article

C2 - 23222960

AN - SCOPUS:84871990888

SN - 1061-4036

VL - 45

SP - 109

EP - 113

JO - Nature Genetics

JF - Nature Genetics

IS - 1

ER -

Emergence and global spread of epidemic healthcare-associated Clostridium difficile

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

Access to Document

Fingerprint

Cite this