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Journal of Bacteriology, January 2009, p. 261-277, Vol. 191, No. 1
0021-9193/09/$08.00+0     doi:10.1128/JB.01230-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Genome of Burkholderia cenocepacia J2315, an Epidemic Pathogen of Cystic Fibrosis Patients {triangledown} ,{dagger}

Matthew T. G. Holden,1* Helena M. B. Seth-Smith,1 Lisa C. Crossman,1 Mohammed Sebaihia,1 Stephen D. Bentley,1 Ana M. Cerdeño-Tárraga,1 Nicholas R. Thomson,1 Nathalie Bason,1 Michael A. Quail,1 Sarah Sharp,1 Inna Cherevach,1 Carol Churcher,1 Ian Goodhead,1,{ddagger} Heidi Hauser,1 Nancy Holroyd,1 Karen Mungall,1 Paul Scott,1 Danielle Walker,1 Brian White,1 Helen Rose,2 Pernille Iversen,3 Dalila Mil-Homens,4 Eduardo P. C. Rocha,5,6 Arsenio M. Fialho,4 Adam Baldwin,7 Christopher Dowson,7 Bart G. Barrell,1 John R. Govan,8 Peter Vandamme,9 C. Anthony Hart,10 Eshwar Mahenthiralingam,2 and Julian Parkhill1

The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Cambridge CB10 1SA, United Kingdom,1 Cardiff School of Biosciences, University of Cardiff, Cardiff CF10 3TL, United Kingdom,2 Department of Molecular Biology, University of Copenhagen, Ole Maaloes Vej 5, 2200 Copenhagen N, Denmark,3 IBB-Institute for Biotechnology and Bioengineering, Center for Biological and Chemical Engineering, Instituto Superior Técnico, Lisbon 1049-001, Portugal,4 UPMC University of Paris 06, Atelier de BioInformatique, F-75005 Paris, France,5 Institut Pasteur, Microbial Evolutionary Genomics, CNRS, URA2171, F-75015 Paris, France,6 Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom,7 University of Edinburgh Medical School, Little France Crescent, Edinburgh EH16 4SB, United Kingdom,8 Laboratorium voor Microbiologie, Universiteit Gent, Ledeganckstraat 35, B-9000 Ghent, Belgium,9 Division of Medical Microbiology, University of Liverpool, Daulby Street, Liverpool L69 3GA, United Kingdom,10

Received 3 September 2008/ Accepted 27 September 2008

Bacterial infections of the lungs of cystic fibrosis (CF) patients cause major complications in the treatment of this common genetic disease. Burkholderia cenocepacia infection is particularly problematic since this organism has high levels of antibiotic resistance, making it difficult to eradicate; the resulting chronic infections are associated with severe declines in lung function and increased mortality rates. B. cenocepacia strain J2315 was isolated from a CF patient and is a member of the epidemic ET12 lineage that originated in Canada or the United Kingdom and spread to Europe. The 8.06-Mb genome of this highly transmissible pathogen comprises three circular chromosomes and a plasmid and encodes a broad array of functions typical of this metabolically versatile genus, as well as numerous virulence and drug resistance functions. Although B. cenocepacia strains can be isolated from soil and can be pathogenic to both plants and man, J2315 is representative of a lineage of B. cenocepacia rarely isolated from the environment and which spreads between CF patients. Comparative analysis revealed that ca. 21% of the genome is unique in comparison to other strains of B. cenocepacia, highlighting the genomic plasticity of this species. Pseudogenes in virulence determinants suggest that the pathogenic response of J2315 may have been recently selected to promote persistence in the CF lung. The J2315 genome contains evidence that its unique and highly adapted genetic content has played a significant role in its success as an epidemic CF pathogen.

* Corresponding author. Mailing address: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, United Kingdom. Phone: 44 (0)1223 494975. Fax: 44 (0)1223 494919. E-mail: mh3{at}sanger.ac.uk

{triangledown} Published ahead of print on 17 October 2008.

{dagger} Supplemental material for this article may be found at http://jb.asm.org/.

{ddagger} Present address: School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, United Kingdom.

Journal of Bacteriology, January 2009, p. 261-277, Vol. 191, No. 1
0021-9193/09/$08.00+0     doi:10.1128/JB.01230-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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