Microevolutionary analysis of Clostridium difficile genomes to investigate transmission.
BACKGROUND: 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 gener...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2012
|
| _version_ | 1826257775220490240 |
|---|---|
| author | Didelot, X Eyre, D Cule, M Ip, C Ansari, M Griffiths, D Vaughan, A O'Connor, L Golubchik, T Batty, E Piazza, P Wilson, D Bowden, R Donnelly, P Dingle, K Wilcox, M Walker, A Crook, D Peto, T Harding, R |
| author_facet | Didelot, X Eyre, D Cule, M Ip, C Ansari, M Griffiths, D Vaughan, A O'Connor, L Golubchik, T Batty, E Piazza, P Wilson, D Bowden, R Donnelly, P Dingle, K Wilcox, M Walker, A Crook, D Peto, T Harding, R |
| author_sort | Didelot, X |
| collection | OXFORD |
| description | BACKGROUND: 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. |
| first_indexed | 2024-03-06T18:23:30Z |
| format | Journal article |
| id | oxford-uuid:07208198-adae-4926-b253-75b5c1ba24bc |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:23:30Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:07208198-adae-4926-b253-75b5c1ba24bc2022-03-26T09:06:05ZMicroevolutionary analysis of Clostridium difficile genomes to investigate transmission.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:07208198-adae-4926-b253-75b5c1ba24bcEnglishSymplectic Elements at Oxford2012Didelot, XEyre, DCule, MIp, CAnsari, MGriffiths, DVaughan, AO'Connor, LGolubchik, TBatty, EPiazza, PWilson, DBowden, RDonnelly, PDingle, KWilcox, MWalker, ACrook, DPeto, THarding, RBACKGROUND: 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. |
| spellingShingle | Didelot, X Eyre, D Cule, M Ip, C Ansari, M Griffiths, D Vaughan, A O'Connor, L Golubchik, T Batty, E Piazza, P Wilson, D Bowden, R Donnelly, P Dingle, K Wilcox, M Walker, A Crook, D Peto, T Harding, R Microevolutionary analysis of Clostridium difficile genomes to investigate transmission. |
| title | Microevolutionary analysis of Clostridium difficile genomes to investigate transmission. |
| title_full | Microevolutionary analysis of Clostridium difficile genomes to investigate transmission. |
| title_fullStr | Microevolutionary analysis of Clostridium difficile genomes to investigate transmission. |
| title_full_unstemmed | Microevolutionary analysis of Clostridium difficile genomes to investigate transmission. |
| title_short | Microevolutionary analysis of Clostridium difficile genomes to investigate transmission. |
| title_sort | microevolutionary analysis of clostridium difficile genomes to investigate transmission |
| work_keys_str_mv | AT didelotx microevolutionaryanalysisofclostridiumdifficilegenomestoinvestigatetransmission AT eyred microevolutionaryanalysisofclostridiumdifficilegenomestoinvestigatetransmission AT culem microevolutionaryanalysisofclostridiumdifficilegenomestoinvestigatetransmission AT ipc microevolutionaryanalysisofclostridiumdifficilegenomestoinvestigatetransmission AT ansarim microevolutionaryanalysisofclostridiumdifficilegenomestoinvestigatetransmission AT griffithsd microevolutionaryanalysisofclostridiumdifficilegenomestoinvestigatetransmission AT vaughana microevolutionaryanalysisofclostridiumdifficilegenomestoinvestigatetransmission AT oconnorl microevolutionaryanalysisofclostridiumdifficilegenomestoinvestigatetransmission AT golubchikt microevolutionaryanalysisofclostridiumdifficilegenomestoinvestigatetransmission AT battye microevolutionaryanalysisofclostridiumdifficilegenomestoinvestigatetransmission AT piazzap microevolutionaryanalysisofclostridiumdifficilegenomestoinvestigatetransmission AT wilsond microevolutionaryanalysisofclostridiumdifficilegenomestoinvestigatetransmission AT bowdenr microevolutionaryanalysisofclostridiumdifficilegenomestoinvestigatetransmission AT donnellyp microevolutionaryanalysisofclostridiumdifficilegenomestoinvestigatetransmission AT dinglek microevolutionaryanalysisofclostridiumdifficilegenomestoinvestigatetransmission AT wilcoxm microevolutionaryanalysisofclostridiumdifficilegenomestoinvestigatetransmission AT walkera microevolutionaryanalysisofclostridiumdifficilegenomestoinvestigatetransmission AT crookd microevolutionaryanalysisofclostridiumdifficilegenomestoinvestigatetransmission AT petot microevolutionaryanalysisofclostridiumdifficilegenomestoinvestigatetransmission AT hardingr microevolutionaryanalysisofclostridiumdifficilegenomestoinvestigatetransmission |