The Continually Evolving Clostridium difficile Species

Abstract

Clostridium difficile is a spore-forming Gram-positive bacterium that causes chronic diarrhea and sometimes life-threatening disease mainly in elderly and hospitalized patients. The reported incidence of C. difficile infection has changed dramatically over the last decade and has been related to the emergence of distinct clonal lineages that appear more transmissible and cause more severe infection. These include PCR ribotypes 027, 017 and more recently 078. Population biology studies using multilocus sequence typing and whole-genome comparisons has helped to define the C. difficile species into four clonal complexes that include PCR ribotypes 027, 017, 078 and 023, as well as a general grouping of most other PCR ribotypes. Further analysis of strains from diverse sources and geographical origins reveal significant microdiversity of clonal complexes and confirms that C. difficile is continuing to evolve. The study of C. difficile represents a real-time global evolutionary experiment where the pathogen is responding to a range of selective pressures created by human activity and practices in healthcare settings. The advent of whole-genome sequencing coupled with phylogeny (phylogeography and phylohistory) will provide unprecedented detail on the local and global emergence and disappearance of C. difficile clones, and facilitate more rational approaches to disease control. This review will highlight the emergence of virulent C. difficile clones and our current understanding of molecular epidemiology of the species.

Keywords:

• Clostridium difficile
• lineages
• next-generation sequencing
• typing
• virulence

Disclaimer

The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Acknowledgements

The authors wish to acknowledge the Wellcome Trust (grant number 086418) and MRC (grant number PF451) for funding our Clostridium difficile research and the London Clostridium difficile Ribotyping Network for support with ribotyping.

Financial & competing interests disclosure

M Cairns is funded by a Doctoral Research Fellowship award from the National Institute for Health Research. This report is independent research arising from a CSO Healthcare Scientist Award supported by the National Institute for Health Research and the CSO. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

M Cairns is funded by a Doctoral Research Fellowship award from the National Institute for Health Research. This report is independent research arising from a CSO Healthcare Scientist Award supported by the National Institute for Health Research and the CSO. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.