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Comparative genome and phenotypic analysis of Clostridium difficile 027 strains provides insight into the evolution of a hypervirulent bacterium

Richard A Stabler1, Miao He2, Lisa Dawson1, Melissa Martin1, Esmeralda Valiente1, Craig Corton2, Trevor D Lawley2, Mohammed Sebaihia2, Michael A Quail2, Graham Rose2, Dale N Gerding3, Maryse Gibert4, Michel R Popoff4, Julian Parkhill2, Gordon Dougan2 and Brendan W Wren1*

Author affiliations

1 London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK

2 Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK

3 Hines VA Hospital, Hines, IL 60141, USA

4 Institut Pasteur, rue du Dr Roux, 75724, Paris, France

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Citation and License

Genome Biology 2009, 10:R102  doi:10.1186/gb-2009-10-9-r102

Published: 25 September 2009



The continued rise of Clostridium difficile infections worldwide has been accompanied by the rapid emergence of a highly virulent clone designated PCR-ribotype 027. To understand more about the evolution of this virulent clone, we made a three-way genomic and phenotypic comparison of an 'historic' non-epidemic 027 C. difficile (CD196), a recent epidemic and hypervirulent 027 (R20291) and a previously sequenced PCR-ribotype 012 strain (630).


Although the genomes are highly conserved, the 027 genomes have 234 additional genes compared to 630, which may contribute to the distinct phenotypic differences we observe between these strains relating to motility, antibiotic resistance and toxicity. The epidemic 027 strain has five unique genetic regions, absent from both the non-epidemic 027 and strain 630, which include a novel phage island, a two component regulatory system and transcriptional regulators.


A comparison of a series of 027 isolates showed that some of these genes appeared to have been gained by 027 strains over the past two decades. This study provides genetic markers for the identification of 027 strains and offers a unique opportunity to explain the recent emergence of a hypervirulent bacterium.