Vaccine 22S (2004) S5–S8 Genetic characterization of methicillin-resistant Staphylococcus aureus Keiichi Hiramatsu * , Shinya Watanabe, Fumihiko Takeuchi, Teruyo Ito, Tadashi Baba Departmentof Bacteriology, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, Japan 113-8421 Available online 11 September 2004 Abstract The genome structure of Staphylococcus aureus is analyzed. The genome is composed of two domains. The first domain, descendent from an ancestral bacterial species, contains house-keeping genes that showed highest homology to those of Bacillus species. The second domain contained the genes responsible for virulence and drug-resistance in human infection that seems to have been acquired from other bacterial species via lateral gene transfer. The latter domain constitutes the genetic information that makes S. aureus a notorious hospital pathogen. © 2004 Elsevier Ltd. All rights reserved. Keywords: Staphylococcus aureus; MRSA; Genome 1. Introduction Staphylococcus aureus is a prominent member of our nat- ural flora. Once the body defense declines, S. aureus behaves as a potent invader of our body causing such infections as en- docarditis, osteomyelitis, and even severe pneumonia. It has considerable pathogenic potential and legendary capability in the acquisition of antibiotic resistance. At the turn of 21st cen- tury, S. aureus genome sequence has finally been uncovered, and researchers started to use the genetic information towards the goal of preventing and treating the infection caused by the organism. Here, I shall briefly describe the characteristics of S. aureus genome that explains its biological potential for virulence and antibiotic resistance. 2. Vertically and laterally transmitted chromosomal domains S. aureus genome is composed of two domains: the first domain is inherited from an ancestral organism; and the second is acquired through horizontal genetic transfer. The genes present in the vertically transmitted domain are mostly house-keeping in nature, and find their closest homologues * Corresponding author. Tel.: +81 3 5802 1040; fax: +81 3 5684 7830. E-mail address: hiram@med.juntendo.ac.jp (K. Hiramatsu). in the Bacillus species [1]. This signifies that Staphylococ- cus species shared a common ancestor with Bacillus species. The phylogenetic relationship estimated by 16S ribosomal sequences agrees with this observation on close evolutionary relationship between the two genera. As many as 52% of S. aureus genes find the closest homologues in either Bacillus subtilis or halodurans among many bacterial species whose entire nucleotide sequences have been determined [1]. Sequence comparison of two S. aureus chromosomes, N315 and MW2 [2], with S. epidermidis and Bacillus sub- tilis genomes showed that the two aureus strains are closely related throughout the chromosome. Sequences of S. aureus and S. epidermidis were homologous from 2 to 10 o’clock of the circular chromosome, whereas the homology of the rest of the chromosome was not significant (in preparation). Al- though the extent of homology was marginal, S. aureus and B. subtilis still showed certain degrees of homology from 3 to 9 o’clock of the circular chromosome. The domain inherited from the common ancestor of Staphylococcus and Bacillus species corresponds to this part of the chromosome, and con- tains most of the house-keeping genes (Fig. 1). The other genomic domain on the chromosome seems to have been acquired from other bacterial species by lateral gene transfer. Though not much is known about transfer mechanisms, the genes in the domain evidently are de- rived from other bacterial species, known from their atyp- ical codon usage pattern and GC content. The domain is 0264-410X/$ – see front matter © 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2004.08.009