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Recombinational switching of the Clostridium difficile S-Layer and a novel glycosylation gene cluster revealed by large-scale whole-genome sequencing

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Dingle, Kate E., Didelot, Xavier, Ansari, M. Azim, Eyre, David W., Vaughan, Alison, Griffiths, David, Ip, Camilla L. C., Batty, Elizabeth M., Golubchik, Tanya, Bowden, Rory, Jolley, Keith A., Hood, Derek W., Fawley, Warren N., Walker, A. Sarah, Peto, Timothy E., Wilcox, Mark H. and Crook, Derrick W. (2012) Recombinational switching of the Clostridium difficile S-Layer and a novel glycosylation gene cluster revealed by large-scale whole-genome sequencing. The Journal of Infectious Diseases, 207 (4). pp. 675-686. doi:10.1093/infdis/jis734

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Official URL: http://dx.doi.org/10.1093/infdis/jis734

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Abstract

Background. Clostridium difficile is a major cause of nosocomial diarrhea, with 30-day mortality reaching 30%. The cell surface comprises a paracrystalline proteinaceous S-layer encoded by the slpA gene within the cell wall protein (cwp) gene cluster. Our purpose was to understand the diversity and evolution of slpA and nearby genes also encoding immunodominant cell surface antigens.

Methods. Whole-genome sequences were determined for 57 C. difficile isolates representative of the population structure and different clinical phenotypes. Phylogenetic analyses were performed on their genomic region (>63 kb) spanning the cwp cluster.

Results. Genetic diversity across the cwp cluster peaked within slpA, cwp66 (adhesin), and secA2 (secretory translocase). These genes formed a 10-kb cassette, of which 12 divergent variants were found. Homologous recombination involving this cassette caused it to associate randomly with genotype. One cassette contained a novel insertion (length, approximately 24 kb) that resembled S-layer glycosylation gene clusters.

Conclusions. Genetic exchange of S-layer cassettes parallels polysaccharide capsular switching in other species. Both cause major antigenic shifts, while the remainder of the genome is unchanged. C. difficile genotype is therefore not predictive of antigenic type. S-layer switching and immune escape could help explain temporal and geographic variation in C. difficile epidemiology and may inform genotyping and vaccination strategies.

Item Type: Journal Article
Divisions: Faculty of Science > Life Sciences (2010- )
Journal or Publication Title: The Journal of Infectious Diseases
Publisher: Oxford University Press
ISSN: 0022-1899
Official Date: 29 November 2012
Dates:
DateEvent
29 November 2012Published
18 September 2012Accepted
Volume: 207
Number: 4
Page Range: pp. 675-686
DOI: 10.1093/infdis/jis734
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access

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