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Journal of Bacteriology, November 2005, p. 7292-7308, Vol. 187, No. 21
0021-9193/05/$08.00+0     doi:10.1128/JB.187.21.7292-7308.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Whole-Genome Sequencing of Staphylococcus haemolyticus Uncovers the Extreme Plasticity of Its Genome and the Evolution of Human-Colonizing Staphylococcal Species

Fumihiko Takeuchi,1 Shinya Watanabe,1 Tadashi Baba,1 Harumi Yuzawa,1,{dagger} Teruyo Ito,1 Yuh Morimoto,1 Makoto Kuroda,1,{ddagger} Longzhu Cui,1 Mikio Takahashi,2 Akiho Ankai,2 Shin-ichi Baba,2 Shigehiro Fukui,2 Jean C. Lee,3 and Keiichi Hiramatsu1*

Department of Microbiology and Infection Control Science, Juntendo University, Tokyo 113-8421, Japan,1 National Institute of Technology and Evaluation, Miyagi 983-0833, Japan,2 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 021153

Received 15 April 2005/ Accepted 4 August 2005

Staphylococcus haemolyticus is an opportunistic bacterial pathogen that colonizes human skin and is remarkable for its highly antibiotic-resistant phenotype. We determined the complete genome sequence of S.haemolyticus to better understand its pathogenicity and evolutionary relatedness to the other staphylococcal species. A large proportion of the open reading frames in the genomes of S.haemolyticus, Staphylococcus aureus, and Staphylococcus epidermidis were conserved in their sequence and order on the chromosome. We identified a region of the bacterial chromosome just downstream of the origin of replication that showed little homology among the species but was conserved among strains within a species. This novel region, designated the "oriC environ," likely contributes to the evolution and differentiation of the staphylococcal species, since it was enriched for species-specific nonessential genes that contribute to the biological features of each staphylococcal species. A comparative analysis of the genomes of S.haemolyticus, S.aureus, and S.epidermidis elucidated differences in their biological and genetic characteristics and pathogenic potentials. We identified as many as 82 insertion sequences in the S.haemolyticus chromosome that probably mediated frequent genomic rearrangements, resulting in phenotypic diversification of the strain. Such rearrangements could have brought genomic plasticity to this species and contributed to its acquisition of antibiotic resistance.

* Corresponding author. Mailing address: 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421 Japan. Phone: 81-3-5802-1040. Fax: 81-3-5684-7830. E-mail: hiram{at}med.juntendo.ac.jp.

{dagger} Present address: Laboratory of Social Genome Science, Department of Medical Genome Science, Graduate School of Frontier Science, University of Tokyo, Tokyo 108-8639, Japan.

{ddagger} Present address: Department of Microbiology, University of Tsukuba, Ibaraki 305-8575, Japan.

Journal of Bacteriology, November 2005, p. 7292-7308, Vol. 187, No. 21
0021-9193/05/$08.00+0     doi:10.1128/JB.187.21.7292-7308.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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