Emergence and global spread of epidemic healthcare-associated Clostridium difficile.
Miao He,Fabio Miyajima,Paul Roberts,Louise Ellison,Derek Pickard,Melissa J. Martin,Thomas R. Connor,Simon R. Harris,Derek Fairley,Kathleen B. Bamford,Kathleen B. Bamford,Stephanie d’Arc,Stephanie d’Arc,Jon S. Brazier,Derek J. Brown,J. E. Coia,Gill Douce,Dale N. Gerding,Heejung Kim,Tse Hsien Koh,Haru Kato,Mitsutoshi Senoh,Tom Louie,Stephen L. Michell,Emma Butt,Sharon J. Peacock,Nicholas M. Brown,Nicholas M. Brown,Thomas V. Riley,Glen Songer,Mark H. Wilcox,Munir Pirmohamed,Ed J. Kuijper,Peter M. Hawkey,Brendan W. Wren,Gordon Dougan,Julian Parkhill,Trevor D. Lawley +37 more
TLDR
This 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.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.read more
Citations
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Clostridium difficile Infection
TL;DR: This article reviews the pathogenesis, epidemiology, diagnosis, and treatment of this nosocomial and potentially fatal infectious diarrhea, as well as the associated risk factors.
Journal ArticleDOI
Understanding the mechanisms and drivers of antimicrobial resistance
Alison Holmes,Luke S. P. Moore,Arnfinn Sundsfjord,Arnfinn Sundsfjord,Martin Steinbakk,Sadie Regmi,Abhilasha Karkey,Philippe J Guerin,Laura J. V. Piddock +8 more
TL;DR: In this paper, the authors proposed a framework to combat the threat to human health and biosecurity from antimicrobial resistance, an understanding of its mechanisms and drivers is needed.
Antimicrobials: access and sustainable eff ectiveness 2 Understanding the mechanisms and drivers of antimicrobial resistance
Alison Holmes,Luke Sp Moore,Martin Steinbakk,Sadie Regmi,Philippe J Guerin,Laura J. V. Piddock +5 more
TL;DR: To combat the threat to human health and biosecurity from antimicrobial resistance, an understanding of its mechanisms and drivers is needed, and broad ranging, multidisciplinary research is needed across these five levels.
Journal ArticleDOI
Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans
Iñaki Comas,Mireia Coscolla,Mireia Coscolla,Tao Luo,Sonia Borrell,Sonia Borrell,Kathryn E. Holt,Midori Kato-Maeda,Julian Parkhill,Bijaya Malla,Bijaya Malla,Stefan Berg,Guy E. Thwaites,Dorothy Yeboah-Manu,Graham H. Bothamley,Jian Mei,Lan-Hai Wei,Stephen D. Bentley,Simon R. Harris,Stefan Niemann,Roland Diel,Abraham Aseffa,Qian Gao,Douglas B. Young,Douglas B. Young,Sebastien Gagneux,Sebastien Gagneux +26 more
TL;DR: Coalescent analyses indicate that MTBC emerged about 70,000 years ago, accompanied migrations of anatomically modern humans out of Africa and expanded as a consequence of increases in human population density during the Neolithic period, consistent with MTBC displaying characteristics indicative of adaptation to both low and high host densities.
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