Research article

Comparative genomic analyses of Streptococcus mutans provide insights into chromosomal shuffling and species-specific content

Fumito Maruyama^1,3 , Mitsuhiko Kobata² , Ken Kurokawa³ , Keishin Nishida⁴ , Atsuo Sakurai² , Kazuhiko Nakano² , Ryota Nomura² , Shigetada Kawabata⁵ , Takashi Ooshima² , Kenta Nakai⁴ , Masahira Hattori⁶ , Shigeyuki Hamada⁷ and Ichiro Nakagawa^1,8

¹Division of Bacteriology, Department of Infectious Diseases Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan

²Department of Pediatric Dentistry, Osaka University Graduate School of Dentistry, 1-8 Yamada-oka, Suita, Osaka 565-0871, Japan

³Divison of Information Biotechnology, Department of Bioinformation Engineering, Tokyo Institute of Technology School and Graduate School of Bioscience and Biotechnology, 4259 Nagatsuta-cho, Midori-ku, Yokohama Kanagawa 226-8501, Japan

⁴Human genome Center, Institute of Medical Science, The University of Tokyo

⁵Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka, 565-0871, Japan

⁶Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8561, Japan

⁷Research Collaboration Center on Emerging and Reemerging Infections (RCC-ERI) 6F, Department of Medical Sciences, Ministry of Public Health, Tiwanon Road, Muang Nonthaburi, 11000, Thailand

⁸Section of Bacterial Pathogenesis, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan

author email corresponding author email

BMC Genomics 2009, 10:358doi:10.1186/1471-2164-10-358

Published:	5 August 2009

Abstract

Background

Streptococcus mutans is the major pathogen of dental caries, and it occasionally causes infective endocarditis. While the pathogenicity of this species is distinct from other human pathogenic streptococci, the species-specific evolution of the genus Streptococcus and its genomic diversity are poorly understood.

Results

We have sequenced the complete genome of S. mutans serotype c strain NN2025, and compared it with the genome of UA159. The NN2025 genome is composed of 2,013,587 bp, and the two strains show highly conserved core-genome. However, comparison of the two S. mutans strains showed a large genomic inversion across the replication axis producing an X-shaped symmetrical DNA dot plot. This phenomenon was also observed between other streptococcal species, indicating that streptococcal genetic rearrangements across the replication axis play an important role in Streptococcus genetic shuffling. We further confirmed the genomic diversity among 95 clinical isolates using long-PCR analysis. Genomic diversity in S. mutans appears to occur frequently between insertion sequence (IS) elements and transposons, and these diversity regions consist of restriction/modification systems, antimicrobial peptide synthesis systems, and transporters. S. mutans may preferentially reject the phage infection by clustered regularly interspaced short palindromic repeats (CRISPRs). In particular, the CRISPR-2 region, which is highly divergent between strains, in NN2025 has long repeated spacer sequences corresponding to the streptococcal phage genome.

Conclusion

These observations suggest that S. mutans strains evolve through chromosomal shuffling and that phage infection is not needed for gene acquisition. In contrast, S. pyogenes tolerates phage infection for acquisition of virulence determinants for niche adaptation.