Emergence and global spread of epidemic healthcare-associated Clostridium difficile

被引:568
作者
He, Miao [1 ]
Miyajima, Fabio [2 ,3 ,4 ]
Roberts, Paul [2 ,3 ,4 ]
Ellison, Louise [1 ]
Pickard, Derek J. [1 ]
Martin, Melissa J. [5 ]
Connor, Thomas R. [1 ]
Harris, Simon R. [1 ]
Fairley, Derek [6 ]
Bamford, Kathleen B. [7 ,8 ]
D'Arc, Stephanie [7 ,8 ]
Brazier, Jon [9 ]
Brown, Derek [10 ]
Coia, John E. [10 ]
Douce, Gill [10 ]
Gerding, Dale [11 ]
Kim, Hee Jung [12 ]
Koh, Tse Hsien [13 ]
Kato, Haru [14 ]
Senoh, Mitsutoshi [14 ]
Louie, Tom [15 ]
Michell, Stephen [16 ]
Butt, Emma [16 ]
Peacock, Sharon J. [17 ,18 ,19 ]
Brown, Nick M. [18 ,19 ]
Riley, Tom [20 ]
Songer, Glen [21 ]
Wilcox, Mark [22 ]
Pirmohamed, Munir [3 ,4 ]
Kuijper, Ed [23 ]
Hawkey, Peter [24 ]
Wren, Brendan W. [5 ]
Dougan, Gordon [1 ]
Parkhill, Julian [1 ]
Lawley, Trevor D. [1 ]
机构
[1] Wellcome Trust Sanger Inst, Cambridge, England
[2] Univ Liverpool, Dept Mol & Clin Pharmacol, Liverpool L69 3BX, Merseyside, England
[3] Royal Liverpool & Broadgreen Univ Hosp Natl Hlth, Liverpool, Merseyside, England
[4] Univ Liverpool, Liverpool L69 3BX, Merseyside, England
[5] London Sch Hyg & Trop Med, Dept Pathogen Mol Biol, London WC1, England
[6] Belfast Hlth & Social Trust, Belfast, Antrim, North Ireland
[7] Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis & Immun, London, England
[8] Imperial Coll Healthcare NHS Trust, Dept Bacteriol, London, England
[9] Anaerob Reference Lab, Cardiff, S Glam, Wales
[10] Scottish Salmonella Shigella & Clostridium Diffic, Glasgow, Lanark, Scotland
[11] Hines VA Hosp, Hines, IL USA
[12] Yonsei Univ, Coll Med, Seoul, South Korea
[13] Singapore Gen Hosp, Dept Pathol, Singapore 0316, Singapore
[14] Natl Inst Infect Dis, Dept Bacteriol, Tokyo, Japan
[15] Univ Calgary, Dept Microbiol Immunol & Infect Dis, Calgary, AB, Canada
[16] Univ Exeter, Coll Life & Environm Sci, Exeter, Devon, England
[17] Univ Cambridge, Dept Med, Cambridge CB2 2QQ, England
[18] Cambridge Univ Hosp NHS Fdn Trust, Cambridge, England
[19] Hlth Protect Agcy, London, England
[20] Univ Western Australia, Sch Pathol & Lab Med, Crawley, WA, Australia
[21] Iowa State Univ, Dept Vet Microbiol & Prevent Med, Ames, IA USA
[22] Univ Leeds, Healthcare Associate Infect Res Grp, Leeds, W Yorkshire, England
[23] Leiden Univ, Med Ctr, Dept Expt Microbiol, Leiden, Netherlands
[24] Univ Birmingham, Sch Immun & Infect, Birmingham, W Midlands, England
基金
英国惠康基金; 英国医学研究理事会;
关键词
RIBOTYPE; 027; NORTH-AMERICA; GENOME; DISEASE; STRAIN; EVOLUTIONARY; OUTBREAK; TRANSMISSION; MORTALITY; INFECTION;
D O I
10.1038/ng.2478
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:109 / U155
页数:6
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