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Microevolutionary analysis of Clostridium difficile genomes to investigate transmission

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Didelot, Xavier, Eyre, David W., Cule, Madeleine, Ip, Camilla L. C., Ansari, M, Griffiths, David, Vaughan, Alison, O'Connor, Lily, Golubchik, Tanya, Batty, Elizabeth M. et al.
(2012) Microevolutionary analysis of Clostridium difficile genomes to investigate transmission. Genome Biology, 13 (12). R118. doi:10.1186/gb-2012-13-12-r118

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Official URL: http://dx.doi.org/10.1186/gb-2012-13-12-r118

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Abstract

The control of Clostridium difficile infection is a major international healthcare priority, hindered by a limited understanding of transmission epidemiology for these bacteria. However, transmission studies of bacterial pathogens are rapidly being transformed by the advent of next generation sequencing.

Results
Here we sequence whole C. difficile genomes from 486 cases arising over four years in Oxfordshire. We show that we can estimate the times back to common ancestors of bacterial lineages with sufficient resolution to distinguish whether direct transmission is plausible or not. Time depths were inferred using a within-host evolutionary rate that we estimated at 1.4 mutations per genome per year based on serially isolated genomes. The subset of plausible transmissions was found to be highly associated with pairs of patients sharing time and space in hospital. Conversely, the large majority of pairs of genomes matched by conventional typing and isolated from patients within a month of each other were too distantly related to be direct transmissions.

Conclusions
Our results confirm that nosocomial transmission between symptomatic C. difficile cases contributes far less to current rates of infection than has been widely assumed, which clarifies the importance of future research into other transmission routes, such as from asymptomatic carriers. With the costs of DNA sequencing rapidly falling and its use becoming more and more widespread, genomics will revolutionize our understanding of the transmission of bacterial pathogens.

Item Type: Journal Article
Divisions: Faculty of Science > Life Sciences (2010- )
Journal or Publication Title: Genome Biology
Publisher: BioMed Central Ltd.
ISSN: 1474-7596
Official Date: 21 December 2012
Dates:
DateEvent
21 December 2012Published
21 December 2012Accepted
Volume: 13
Number: 12
Article Number: R118
DOI: 10.1186/gb-2012-13-12-r118
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access

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