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Journal of Bacteriology, January 2006, p. 669-676, Vol. 188, No. 2
0021-9193/06/$08.00+0     doi:10.1128/JB.188.2.669-676.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Microarrays Reveal that Each of the Ten Dominant Lineages of Staphylococcus aureus Has a Unique Combination of Surface-Associated and Regulatory Genes{dagger}

Jodi A. Lindsay,1* Catrin E. Moore,2 Nicholas P. Day,3 Sharon J. Peacock,3 Adam A. Witney,4 Richard A. Stabler,4,{ddagger} Sarah E. Husain,4,§ Philip D. Butcher,4 and Jason Hinds4

Centre for Infection, Division of Cellular and Molecular Medicine, St George's, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom,1 Department of Paediatrics, University of Oxford, The John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom,2 Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand,3 Bacterial Microarray Group, Division of Cellular and Molecular Medicine, St George's, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom4

Received 14 July 2005/ Accepted 23 October 2005

Staphylococcus aureus is the most common cause of hospital-acquired infection. In healthy hosts outside of the health care setting, S. aureus is a frequent colonizer of the human nose but rarely causes severe invasive infection such as bacteremia, endocarditis, or osteomyelitis. To identify genes associated with community-acquired invasive isolates, regions of genomic variability, and the S. aureus population structure, we compared 61 community-acquired invasive isolates of S. aureus and 100 nasal carriage isolates from healthy donors using a microarray spotted with PCR products representing every gene from the seven S. aureus sequencing projects. The core genes common to all strains were identified, and 10 dominant lineages of S. aureus were clearly discriminated. Each lineage carried a unique combination of hundreds of "core variable" (CV) genes scattered throughout the chromosome, suggesting a common ancestor but early evolutionary divergence. Many CV genes are regulators of virulence genes or known or predicted to be expressed on the bacterial surface and to interact with the host during nasal colonization and infection. Within each lineage, isolates showed substantial variation in the carriage of mobile genetic elements and their associated virulence and resistance genes, indicating frequent horizontal transfer. However, we were unable to identify any association between lineage or gene and invasive isolates. We suggest that the S. aureus gene combinations necessary for invasive disease may also be necessary for nasal colonization and that community-acquired invasive disease is strongly dependent on host factors.

* Corresponding author. Mailing address: Centre for Infection, Division of Cellular & Molecular Medicine, St George's, University of London, Cranmer Tce, London SW17 0RE, United Kingdom. Phone: 44 (0)208 725 0445. Fax: 44 (0)208 725 3487. E-mail: jlindsay{at}sgul.ac.uk.

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

{ddagger} Present address: Department of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.

§ Present address: Department of Immunology, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom.

Journal of Bacteriology, January 2006, p. 669-676, Vol. 188, No. 2
0021-9193/06/$08.00+0     doi:10.1128/JB.188.2.669-676.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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