Whole genome sequencing of Staphylococcus haemolyticus uncovers extreme plasticity of its genome and dynamism in the evolution of human-colonizing staphylococcal species

Fumihiko Takeuchi1, Shinya Watanabe1, Tadashi Baba1, Harumi Yuzawa1, Teruyo Ito1, Longzhu Cui1, Yuh Morimoto1, Makoto Kuroda1, Mikio Takahashi2, Akiho Ankai2, Shin-ichi Baba2, Shigehiro Fukui2, Jean C. Lee3, Keiichi Hiramatsu1,
1 Juntendo University, Tokyo, Japan
2 National Institute of Technology and Evaluation, Sendai, Japan
3 Brigham and Women's Hospital and Harvard Medical School, Boston, USA

We herein determined the complete genome sequence of human pathogenic bacteria Staphylococcus haemolyticus in order to pursue its pathogenic background and possible mechanisms of its quick acquisition of resistance to many antibiotics. The sequence determination further enabled us to perform comparative analysis with previously sequenced S. aureus and S. epidermidis, former of which is the most virulent species among staphylococci and the latter is the most common colonizer of human skin. Our comparative analysis revealed that 48% of genes were common to the three species. However, we were surprised to find that a region as long as 0.4 Mbp in the downstream of orfX, an open reading frame of unknown function located approximately 30 kbp downstream the replication origin (oriC), was much less conserved among species than other part of the chromosome. We designated this chromosomal region, which has been formed presumably by repeated drastic rearrangements in the past, as "oriC environ." The oriC environ seems to accumulate useful foreign genes and contributes to the formation of species-specific features in each species. In addition, the comparative analysis among three staphylococci also elucidated differences in their biological characteristics and pathogenic potentials. Moreover, in the S. haemolyticus chromosome, we identified as many as 82 insertion sequences that probably mediated frequent genomic rearrangements in the oriC environ, resulting in phenotypic diversification of the strain. Such rearrangements could have brought genomic plasticity to this species and contributed to its quick acquisition of the antibiotic-resistance.