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Journal of Bacteriology, April 2005, p. 2426-2438, Vol. 187, No. 7
0021-9193/05/$08.00+0     doi:10.1128/JB.187.7.2426-2438.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Insights on Evolution of Virulence and Resistance from the Complete Genome Analysis of an Early Methicillin-Resistant Staphylococcus aureus Strain and a Biofilm-Producing Methicillin-Resistant Staphylococcus epidermidis Strain{dagger}

Steven R. Gill,1* Derrick E. Fouts,1 Gordon L. Archer,2 Emmanuel F. Mongodin,1 Robert T. DeBoy,1 Jacques Ravel,1 Ian T. Paulsen,1 James F. Kolonay,1 Lauren Brinkac,1 Mauren Beanan,1 Robert J. Dodson,1 Sean C. Daugherty,1 Ramana Madupu,1 Samuel V. Angiuoli,1 A. Scott Durkin,1 Daniel H. Haft,1 Jessica Vamathevan,1 Hoda Khouri,1 Terry Utterback,1,3 Chris Lee,1 George Dimitrov,1 Lingxia Jiang,1 Haiying Qin,1 Jan Weidman,1 Kevin Tran,1 Kathy Kang,1 Ioana R. Hance,1 Karen E. Nelson,1 and Claire M. Fraser1

The Institute for Genomic Research,1 J. Craig Venter Science Foundation Joint Technology Center, Rockville, Maryland,3 Division of Infectious Diseases, Virginia Commonwealth University Health System, Richmond, Virginia2

Received 27 July 2004/ Accepted 13 December 2004

Staphylococcus aureus is an opportunistic pathogen and the major causative agent of numerous hospital- and community-acquired infections. Staphylococcus epidermidis has emerged as a causative agent of infections often associated with implanted medical devices. We have sequenced the ~2.8-Mb genome of S. aureus COL, an early methicillin-resistant isolate, and the ~2.6-Mb genome of S. epidermidis RP62a, a methicillin-resistant biofilm isolate. Comparative analysis of these and other staphylococcal genomes was used to explore the evolution of virulence and resistance between these two species. The S. aureus and S. epidermidis genomes are syntenic throughout their lengths and share a core set of 1,681 open reading frames. Genome islands in nonsyntenic regions are the primary source of variations in pathogenicity and resistance. Gene transfer between staphylococci and low-GC-content gram-positive bacteria appears to have shaped their virulence and resistance profiles. Integrated plasmids in S. epidermidis carry genes encoding resistance to cadmium and species-specific LPXTG surface proteins. A novel genome island encodes multiple phenol-soluble modulins, a potential S. epidermidis virulence factor. S. epidermidis contains the cap operon, encoding the polyglutamate capsule, a major virulence factor in Bacillus anthracis. Additional phenotypic differences are likely the result of single nucleotide polymorphisms, which are most numerous in cell envelope proteins. Overall differences in pathogenicity can be attributed to genome islands in S. aureus which encode enterotoxins, exotoxins, leukocidins, and leukotoxins not found in S. epidermidis.

* Corresponding author. Mailing address: Microbial Genomics, The Institute for Genomic Research, 9712 Medical Center Dr., Rockville, MD 20850. Phone: (301) 795-7572. Fax: (301) 838-0208. E-mail: srgill{at}tigr.org.

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

Journal of Bacteriology, April 2005, p. 2426-2438, Vol. 187, No. 7
0021-9193/05/$08.00+0     doi:10.1128/JB.187.7.2426-2438.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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