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Nucleic Acids Research, 2003, Vol. 31, No. 22 6516-6523
© 2003 Oxford University Press


Article

The complete genome sequence and analysis of Corynebacterium diphtheriae NCTC13129

A. M. Cerdeño-Tárraga, A. Efstratiou1, L. G. Dover2, M. T. G. Holden, M. Pallen3, S. D. Bentley, G. S. Besra2, C. Churcher, K. D. James, A. De Zoysa1, T. Chillingworth, A. Cronin, L. Dowd, T. Feltwell, N. Hamlin, S. Holroyd, K. Jagels, S. Moule, M. A. Quail, E. Rabbinowitsch, K. M. Rutherford, N. R. Thomson, L. Unwin, S. Whitehead, B. G. Barrell and J. Parkhill*

The Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK, 1 WHO Collaborating Centre for Diphtheria and Streptococcal Infections, PHLS Respiratory and Systemic Infection Laboratory, Central Public Health Laboratory, London NW9 5DF, UK, 2 School of Biosciences and 3 Division of Immunity and Infection, Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK

*To whom correspondence should be addressed. Tel: +44 1223 494975; Fax: +44 1223 494919; Email: parkhill{at}sanger.ac.uk

Corynebacterium diphtheriae is a Gram-positive, non-spore forming, non-motile, pleomorphic rod belonging to the genus Corynebacterium and the actinomycete group of organisms. The organism produces a potent bacteriophage-encoded protein exotoxin, diphtheria toxin (DT), which causes the symptoms of diphtheria. This potentially fatal infectious disease is controlled in many developed countries by an effective immunisation programme. However, the disease has made a dramatic return in recent years, in particular within the Eastern European region. The largest, and still on-going, outbreak since the advent of mass immunisation started within Russia and the newly independent states of the former Soviet Union in the 1990s. We have sequenced the genome of a UK clinical isolate (biotype gravis strain NCTC13129), representative of the clone responsible for this outbreak. The genome consists of a single circular chromosome of 2 488 635 bp, with no plasmids. It provides evidence that recent acquisition of pathogenicity factors goes beyond the toxin itself, and includes iron-uptake systems, adhesins and fimbrial proteins. This is in contrast to Corynebacterium’s nearest sequenced pathogenic relative, Mycobacterium tuberculosis, where there is little evidence of recent horizontal DNA acquisition. The genome itself shows an unusually extreme large-scale compositional bias, being noticeably higher in G+C near the origin than at the terminus.


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