We have completed the genome sequencing of Clostridium difficile strain 630. Strain 630 is multi-drug resistant, and was isolated from a patient with severe PMC that had spread to dozens of other patients on the same ward in Zurich, Switzerland in 1982. Thus strain 630 has the genetic attributes of a fully virulent, highly transmissible, drug resistant strain. This work was carried out in collaboration with Brendan Wren of the London School of Hygiene and Tropical Medicine, Neil Fairweather and Gordon Dougan of the Centre for Molecular Microbiology and Infection, Imperial College, London and Peter Mullany of the Eastman Dental Institute, London.

We are also sequencing several other strains of C. difficile, including C. difficile strain R20291 (SM), C. difficile strain 196, C. difficile strain BI1, C. difficile strain M120 and C. difficile strain M68.

Published Genome Data

Published Sequence

The Sanger Institute has completed the sequencing of Clostridium difficile strain 630 (epidemic type X). The genome consists of a circular chromosome of 4,290,252 bp with a G+C content of 29.06%, and a circular plasmid of 7,881 bp with a G+C content of 27.9%. The fully annotated chromosome and plasmid are available from the EMBL/GenBank databases with accession numbers AM180355 and AM180356 respectively.

Shotgun and assembly data from this project are available from our FTP site.

Comparative 454 Sequence

We have also generated sequence data from C. difficile strain R20291 (SM) using the 454/Roche GS20 system. C. difficile strain R20291 was isolated in Stoke Mandeville, UK, and is closely related to the North American hypervirulent BI strains. The sequence is in 546 contigs with a total size of 4.049 Mb long and may be downloaded from the FTP link on the right.

Please note that this sequence is unchecked and unedited, and will contain errors. The GS20 is known to have problems with homopolymeric tracts, and these are therefore likely to contain significant numbers of errors.

Ongoing Projects

The Sanger Institute has begun shotgun sequencing of seven further strains of C. difficile as follows :

C. difficile strain 196

• Isolated: France, 1985 (Ribotype 027)
• Assembly: 1 contigs >1kb (1 contigs >2kb); total size 4.111 Mb
• Shotgun: 33,509 reads totalling 20.887 Mb, theoretical genome coverage of 99.26%

C. difficile strain BI1

• Isolated: USA, 1988 (Ribotype 027)
• Assembly: 19 contigs >1kb (10 contigs >2kb); total size 4.474 Mb
• Shotgun: 34,428 reads totalling 21.622 Mb, theoretical genome coverage of 99.33%

C. difficile strain M120

   * Isolated: UK, 2007 (Ribotype 078)

   * Assembly: 35 contigs >1kb (20 contigs >2kb); total size 4.104 Mb

   * Shotgun: 32,381 reads totalling 21.754 Mb, theoretical genome coverage of 99.33%

C. difficile strain M68

   * Isolated: Ireland, 2006 (Ribotype 017)

   * Assembly: 814 contigs >1kb (421 contigs >2kb); total size 5.480 Mb

   * Shotgun: 29,958 reads totalling 18.975 Mb, theoretical genome coverage of 98.77%

C. difficile strain SM (R20291)

   * Isolated: UK, 2006 (Ribotype 027)

   * Assembly: 69 contigs >1kb (49 contigs >2kb); total size 4.230 Mb

   * Shotgun: 34,018 reads totalling 22.599 Mb, theoretical genome coverage of 99.45%

C. difficile strain CF5

   * Isolated: Belgium, 1995 (Ribotype 017)

   * Assembly: 42 contigs >1kb (25 contigs >2kb); total size 4.205 Mb

   * Shotgun: 34,226 reads totalling 23.359 Mb, theoretical genome coverage of 99.99%

C. difficile strain 855

   * Isolated: USA, 2007 (Ribotype 027)

   * Assembly: 31 contigs >1kb (22 contigs >2kb); total size 4.220 Mb

   * Shotgun: 33,918 reads totalling 22.907 Mb, theoretical genome coverage of 99.99%

Shotgun and assembly data from these projects are available from our ftp site.

• Evolutionary dynamics of Clostridium difficile over short and long time scales.

  He M, Sebaihia M, Lawley TD, Stabler RA, Dawson LF, Martin MJ, Holt KE, Seth-Smith HM, Quail MA, Rance R, Brooks K, Churcher C, Harris D, Bentley SD, Burrows C, Clark L, Corton C, Murray V, Rose G, Thurston S, van Tonder A, Walker D, Wren BW, Dougan G and Parkhill J

  Proceedings of the National Academy of Sciences of the United States of America 2010;107;16;7527-32

  PUBMED: 20368420; PMC: 2867753; DOI: 10.1073/pnas.0914322107

• Proteomic and genomic characterization of highly infectious Clostridium difficile 630 spores.

  Lawley TD, Croucher NJ, Yu L, Clare S, Sebaihia M, Goulding D, Pickard DJ, Parkhill J, Choudhary J and Dougan G

  Journal of bacteriology 2009;191;17;5377-86

  PUBMED: 19542279; PMC: 2725610; DOI: 10.1128/JB.00597-09

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

  Stabler RA, He M, Dawson L, Martin M, Valiente E, Corton C, Lawley TD, Sebaihia M, Quail MA, Rose G, Gerding DN, Gibert M, Popoff MR, Parkhill J, Dougan G and Wren BW

  Genome biology 2009;10;9;R102

  PUBMED: 19781061; PMC: 2768977; DOI: 10.1186/gb-2009-10-9-r102