Skip to main content

Advertisement

SpringerLink
Log in

Exploring the Genomic Diversity and Cariogenic Differences of Streptococcus mutans Strains Through Pan-Genome and Comparative Genome Analysis

  • Published:
Current Microbiology Aims and scope Submit manuscript

Abstract

Pan-genome refers to the sum of genes that can be found in a given bacterial species, including the core-genome and the dispensable genome. In this study, the genomes from 183 Streptococcus mutans (S. mutans) isolates were analyzed from the pan-genome perspective. This analysis revealed that S. mutans has an “open” pan-genome, implying that there are plenty of new genes to be found as more genomes are sequenced. Additionally, S. mutans has a limited core-genome, which is composed of genes related to vital activities within the bacterium, such as metabolism and hereditary information storage or processing, occupying 35.6 and 26.6% of the core genes, respectively. We estimate the theoretical core-genome size to be about 1083 genes, which are fewer than other Streptococcus species. In addition, core genes suffer larger selection pressures in comparison to those that are less widely distributed. Not surprisingly, the distribution of putative virulence genes in S. mutans strains does not correlate with caries status, indicating that other factors are also responsible for cariogenesis. These results contribute to a more understanding of the evolutionary characteristics and dynamic changes within the genome components of the species. This also helps to form a new theoretical foundation for preventing dental caries. Furthermore, this study sets an example for analyzing large genomic datasets of pathogens from the pan-genome perspective.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price includes VAT (France)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

References

  1. Aikawa C, Furukawa N, Watanabe T et al (2012) Complete genome sequence of the serotype k Streptococcus mutans strain LJ23. J Bacteriol 194:2754–2755. doi:10.1128/JB.00350-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ajdić D, McShan WM, McLaughlin RE et al (2002) Genome sequence of Streptococcus mutans UA159, a cariogenic dental pathogen. Proc Natl Acad Sci USA 99:14434–14439. doi:10.1073/pnas.172501299

    Article  PubMed  PubMed Central  Google Scholar 

  3. Alm E, Huang K, Arkin A (2006) The evolution of two-component systems in bacteria reveals different strategies for niche adaptation. PLoS Comput Biol 2:e143. doi:10.1371/journal.pcbi.0020143

    Article  PubMed  PubMed Central  Google Scholar 

  4. Argimón S, Caufield PW (2011) Distribution of putative virulence genes in Streptococcus mutans strains does not correlate with caries experience. J Clin Microbiol 49:984–992. doi:10.1128/JCM.01993-10

    Article  PubMed  PubMed Central  Google Scholar 

  5. Argimón S, Konganti K, Chen H et al (2014) Comparative genomics of oral isolates of Streptococcus mutans by in silico genome subtraction does not reveal accessory DNA associated with severe early childhood caries. Infect Genet Evol 21:269–278. doi:10.1016/j.meegid.2013.11.003

    Article  PubMed  Google Scholar 

  6. Arthur RA, Cury AADB, Graner ROM et al (2011) Genotypic and phenotypic analysis of S. mutans isolated from dental biofilms formed in vivo under high cariogenic conditions. Braz Dent J 22:267–274

    Article  PubMed  Google Scholar 

  7. Bender GR, Sutton SV, Marquis RE (1986) Acid tolerance, proton permeabilities, and membrane ATPases of oral streptococci. Infect Immun 53:331–338

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Biswas S, Biswas I (2012) Complete genome sequence of Streptococcus mutans GS-5, a serotype c strain. J Bacteriol 194:4787–4788. doi:10.1128/JB.01106-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bowen WH, Schilling K, Giertsen E et al (1991) Role of a cell surface-associated protein in adherence and dental caries. Infect Immun 59:4606–4609

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Boyd DA, Cvitkovitch DG, Bleiweis AS et al (2000) Defects in D-alanyl-lipoteichoic acid synthesis in Streptococcus mutans results in acid sensitivity. J Bacteriol 182:6055–6065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Burne RA (1998) Oral streptococci. products of their environment. J Dent Res 77:445. doi:10.1177/00220345980770030301

    Article  CAS  PubMed  Google Scholar 

  12. Burne RA, Chen YY, Wexler DL et al (1996) Cariogenicity of Streptococcus mutans strains with defects in fructan metabolism assessed in a program-fed specific-pathogen-free rat model. J Dent Res 75:1572–1577. doi:10.1177/00220345960750080801

    Article  CAS  PubMed  Google Scholar 

  13. Cheon K, Moser SA, Whiddon J et al (2011) Genetic diversity of plaque mutans streptococci with rep-PCR. J Dent Res 90:331–335. doi:10.1177/0022034510386375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Conrads G, de Soet JJ, Song L et al (2014) Comparing the cariogenic species Streptococcus sobrinus and S. mutans on whole genome level. J Oral Microbiol 6:26189. doi:10.3402/jom.v6.26189

    Article  PubMed  Google Scholar 

  15. Cornejo OE, Lefébure T, Bitar PDP et al (2013) Evolutionary and population genomics of the cavity causing bacteria Streptococcus mutans. Mol Biol Evol 30:881–893. doi:10.1093/molbev/mss278

    Article  CAS  PubMed  Google Scholar 

  16. Delcher AL, Bratke KA, Powers EC et al (2007) Identifying bacterial genes and endosymbiont DNA with Glimmer. Bioinformatics 23:673–679. doi:10.1093/bioinformatics/btm009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Deng W, Wang Y, Liu Z et al (2014) HemI: a toolkit for illustrating heatmaps. PLoS ONE 9:e111988. doi:10.1371/journal.pone.0111988

    Article  PubMed  PubMed Central  Google Scholar 

  18. Dintilhac A, Claverys JP (1997) The adc locus, which affects competence for genetic transformation in Streptococcus pneumoniae, encodes an ABC transporter with a putative lipoprotein homologous to a family of streptococcal adhesins. Res Microbiol 148:119–131. doi:10.1016/S0923-2508(97)87643-7

    Article  CAS  PubMed  Google Scholar 

  19. Dunning DW, McCall LW, Powell WF et al (2008) SloR modulation of the Streptococcus mutans acid tolerance response involves the GcrR response regulator as an essential intermediary. Microbiology 154:1132–1143. doi:10.1099/mic.0.2007/012492-0

    Article  CAS  PubMed  Google Scholar 

  20. Enright AJ, Van Dongen S, Ouzounis CA (2002) An efficient algorithm for large-scale detection of protein families. Nucleic Acids Res 30:1575–1584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Fan MW, Bian Z, Peng ZX et al (2002) A DNA vaccine encoding a cell-surface protein antigen of Streptococcus mutans protects gnotobiotic rats from caries. J Dent Res 81:784. doi:10.1177/0810784

    Article  CAS  PubMed  Google Scholar 

  22. Fischer S, Brunk BP, Chen F et al (2011) Using OrthoMCL to assign proteins to OrthoMCL‐DB groups or to cluster proteomes into new Ortholog groups. Curr Protoc Bioinform 35:6.12.1–6.12.19. doi:10.1002/0471250953.bi0612s35

    Google Scholar 

  23. Fraser-Liggett CM (2005) Insights on biology and evolution from microbial genome sequencing. Genome Res 15:1603–1610. doi:10.1101/gr.3724205

    Article  CAS  PubMed  Google Scholar 

  24. Gogarten JP, Townsend JP (2005) Horizontal gene transfer, genome innovation and evolution. Nat Rev Microbiol 3:679–687. doi:10.1038/nrmicro1204

    Article  CAS  PubMed  Google Scholar 

  25. Gutierrez JA, Crowley PJ, Cvitkovitch DG et al (1999) Streptococcus mutans ffh, a gene encoding a homologue of the 54 kDa subunit of the signal recognition particle, is involved in resistance to acid stress. Microbiology 145:357–366. doi:10.1099/13500872-145-2-357

    Article  CAS  PubMed  Google Scholar 

  26. Hamada S, Slade HD (1980) Biology, immunology, and cariogenicity of streptococcus mutans. Microbiol Rev 44:331

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Hale JD, Ting YT, Jack RW et al (2005) Bacteriocin (mutacin) production by Streptococcus mutans genome sequence reference strain UA159: elucidation of the antimicrobial repertoire by genetic dissection. Appl Environ Microbiol 71:7613. doi:10.1128/AEM.71.11.7613-7617.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Harper DS, Loesche WJ (1984) Growth and acid tolerance of human dental plaque bacteria. Arch Oral Biol 29:843–848

    Article  CAS  PubMed  Google Scholar 

  29. Heaps HS (1978) Information retrieval: computational and theoretical aspects. Academic Press, New York

    Google Scholar 

  30. Hiller NL, Janto B, Hogg JS et al (2007) Comparative genomic analyses of seventeen Streptococcus pneumoniae strains: insights into the pneumococcal supragenome. J Bacteriol 189:8186–8195. doi:10.1128/JB.00690-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Hogg JS, Hu FZ, Janto B et al (2007) Characterization and modeling of the Haemophilus influenzae core and supragenomes based on the complete genomic sequences of Rd and 12 clinical nontypeable strains. Genome Biol 8:R103. doi:10.1186/gb-2007-8-6-r103

    Article  PubMed  PubMed Central  Google Scholar 

  32. Hossain MS, Biswas I (2012) An extracelluar protease, SepM, generates functional competence-stimulating peptide in Streptococcus mutans UA159. J Bacteriol 194:5886–5896. doi:10.1128/JB.01381-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kreikemeyer B, McIver KS, Podbielski A (2003) Virulence factor regulation and regulatory networks in Streptococcus pyogenes and their impact on pathogen–host interactions. Trends Microbiol 11:224–232

    Article  CAS  PubMed  Google Scholar 

  34. Krishnan K, Chen T, Paster BJ (2016) A practical guide to the oral microbiome and its relation to health and disease. Oral Dis 23:276. doi:10.1111/odi.12509

    Article  PubMed  Google Scholar 

  35. Kryazhimskiy S, Plotkin JB (2008) The population genetics of dN/dS. PLoS Genet 4:e1000304. doi:10.1371/journal.pgen.1000304

    Article  PubMed  PubMed Central  Google Scholar 

  36. Lagesen K, Hallin P, Rødland EA et al (2007) RNAmmer: consistent and rapid annotation of ribosomal RNA genes. Nucleic Acids Res 35:3100–3108. doi:10.1093/nar/gkm160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Lefébure T, Stanhope MJ (2007) Evolution of the core and pan-genome of Streptococcus: positive selection, recombination, and genome composition. Genome Biol 8:R71. doi:10.1186/gb-2007-8-5-r71

    Article  PubMed  PubMed Central  Google Scholar 

  38. Lemos JA, Luzardo Y, Burne RA (2007) Physiologic effects of forced down-regulation of dnaK and groEL expression in Streptococcus mutans. J Bacteriol 189:1582–1588. doi:10.1128/JB.01655-06

    Article  CAS  PubMed  Google Scholar 

  39. Liao Y, Chen J, Brandt BW et al (2015) Identification and functional analysis of genome mutations in a fluoride-resistant Streptococcus mutans strain. PLoS ONE 10:e0122630. doi:10.1371/journal.pone.0122630

    Article  PubMed  PubMed Central  Google Scholar 

  40. Loesche WJ (1986) Role of Streptococcus mutans in human dental decay. Microbiol Rev 50:353–380

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Lowe TM, Eddy SR (1997) tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequence. Nucleic Acids Res 25:955–964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Luo R, Liu B, Xie Y et al (2012) SOAPdenovo2: an empirically improved memory-efficient short-read de novo assembler. Gigascience 1:18. doi:10.1186/2047-217X-1-18

    Article  PubMed  PubMed Central  Google Scholar 

  43. Marri PR, Hao W, Golding GB (2006) Gene gain and gene loss in streptococcus: is it driven by habitat? Mol Biol Evol 23:2379–2391. doi:10.1093/molbev/msl115

    Article  CAS  PubMed  Google Scholar 

  44. Martinez-Medina M, Aldeguer X, Lopez-Siles M et al (2009) Molecular diversity of Escherichia coli in the human gut: new ecological evidence supporting the role of adherent-invasive E. coli (AIEC) in Crohn’s disease. Inflamm Bowel Dis 15:872–882. doi:10.1002/ibd.20860

    Article  PubMed  Google Scholar 

  45. Maruyama F, Kobata M, Kurokawa K et al (2009) Comparative genomic analyses of Streptococcus mutans provide insights into chromosomal shuffling and species-specific content. BMC Genom 10:358. doi:10.1186/1471-2164-10-358

    Article  Google Scholar 

  46. Mattos-Graner RO, Napimoga MH, Fukushima K et al (2004) Comparative analysis of Gtf isozyme production and diversity in isolates of Streptococcus mutans with different biofilm growth phenotypes. J Clin Microbiol 42:4586–4592. doi:10.1128/JCM.42.10.4586-4592.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Minah GE, Loesche WJ (1977) Sucrose metabolism by prominent members of the flora isolated from cariogenic and non-cariogenic dental plaques. Infect Immun 17:55–61

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Moreno-Hagelsieb G, Latimer K (2008) Choosing BLAST options for better detection of orthologs as reciprocal best hits. Bioinformatics 24:319–324. doi:10.1093/bioinformatics/btm585

    Article  CAS  PubMed  Google Scholar 

  49. Morrison DA (1997) Streptococcal competence for genetic transformation: regulation by peptide pheromones. Microb Drug Resist 3:27. doi:10.1089/mdr.1997.3.27

    Article  CAS  PubMed  Google Scholar 

  50. Muzzi A, Donati C (2011) Population genetics and evolution of the pan-genome of Streptococcus pneumoniae. Int J Med Microbiol 301:619–622. doi:10.1016/j.ijmm.2011.09.008

    Article  CAS  PubMed  Google Scholar 

  51. Nakano K, Nomura R, Matsumoto M et al (2010) Roles of oral bacteria in cardiovascular diseases—from molecular mechanisms to clinical cases: cell-surface structures of novel serotype k Streptococcus mutans strains and their correlation to virulence. J Pharmacol Sci 113:120–125

    Article  CAS  PubMed  Google Scholar 

  52. Nomura R, Nakano K, Taniguchi N et al (2009) Molecular and clinical analyses of the gene encoding the collagen-binding adhesin of Streptococcus mutans. J Med Microbiol 58:469–475. doi:10.1099/jmm.0.007559-0

    Article  CAS  PubMed  Google Scholar 

  53. Ooshima T, Matsumura M, Hoshino T et al (2001) Contributions of three glucosyltransferases to sucrose-dependent adherence of Streptococcus mutans. J Dent Res 80:1672–1677. doi:10.1177/00220345010800071401

    Article  CAS  PubMed  Google Scholar 

  54. Phattarataratip E, Olson B, Broffitt B et al (2011) Streptococcus mutans strains recovered from caries-active or caries-free individuals differ in sensitivity to host antimicrobial peptides. Mol Oral Microbiol 26:187–199. doi:10.1111/j.2041-1014.2011.00607.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Russell MW, Harrington DJ, Russell RR (1995) Identity of Streptococcus mutans surface protein antigen III and wall-associated protein antigen A. Infect Immun 63:733–735

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Song L, Sudhakar P, Wei W et al (2012) A genome-wide study of two-component signal transduction systems in eight newly sequenced mutans streptococci strains. BMC Genom 13:128. doi:10.1186/1471-2164-13-128

    Article  CAS  Google Scholar 

  57. Song L, Wang W, Conrads G et al (2013) Genetic variability of mutans streptococci revealed by wide whole-genome sequencing. BMC Genom 14:430. doi:10.1186/1471-2164-14-430

    Article  CAS  Google Scholar 

  58. Spatafora G, Rohrer K, Barnard D et al (1995) A Streptococcus mutans mutant that synthesizes elevated levels of intracellular polysaccharide is hypercariogenic in vivo. Infect Immun 63:2556–2563

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Staat RH, Langley SD, Doyle RJ (1980) Streptococcus mutans adherence: presumptive evidence for protein-mediated attachment followed by glucan-dependent cellular accumulation. Infect Immun 27:675–681

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Stock AM, Robinson VL, Goudreau PN (2000) Two-component signal transduction. Annu Rev Biochem 69:183–215. doi:10.1146/annurev.biochem.69.1.183

    Article  CAS  PubMed  Google Scholar 

  61. Tamesada M, Kawabata S, Fujiwara T et al (2004) Synergistic effects of streptococcal glucosyltransferases on adhesive biofilm formation. J Dent Res 83:874–879. doi:10.1177/154405910408301110

    Article  CAS  PubMed  Google Scholar 

  62. Tettelin H, Masignani V, Cieslewicz MJ et al (2005) Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial “pan-genome”. Proc Natl Acad Sci USA 102:13950–13955. doi:10.1073/pnas.0506758102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Tettelin H, Riley D, Cattuto C et al (2008) Comparative genomics: the bacterial pan-genome. Curr Opin Microbiol 11:472–477

    Article  CAS  PubMed  Google Scholar 

  64. Valdez RM, Dos Santos VR, Caiaffa KS et al (2016) Comparative in vitro investigation of the cariogenic potential of bifidobacteria. Arch Oral Biol 71:97. doi:10.1016/j.archoralbio.2016.07.005

    Article  CAS  PubMed  Google Scholar 

  65. Van HJ (1994) Role of micro-organisms in caries etiology. J Dent Res 73:672. doi:10.1177/00220345940730031301

    Article  Google Scholar 

  66. Waterhouse JC, Russell RR (2006) Dispensable genes and foreign DNA in Streptococcus mutans. Microbiology 152:1777–1788. doi:10.1099/mic.0.28647-0

    Article  CAS  PubMed  Google Scholar 

  67. Waterhouse JC, Swan DC, Russell RRB (2007) Comparative genome hybridization of Streptococcus mutans strains. Oral Microbiol Immunol 22:103–110. doi:10.1111/j.1399-302X.2007.00330.x

    Article  CAS  PubMed  Google Scholar 

  68. Wu C, Cichewicz R, Li Y et al (2010) Genomic island TnSmu2 of Streptococcus mutans harbors a nonribosomal peptide synthetase-polyketide synthase gene cluster responsible for the biosynthesis of pigments involved in oxygen and H2O2 tolerance. Appl Environ Microbiol 76:5815–5826. doi:10.1128/AEM.03079-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Yamashita Y, Bowen WH, Kuramitsu HK (1992) Molecular analysis of a Streptococcus mutans strain exhibiting polymorphism in the tandem gtfB and gtfC genes. Infect Immun 60:1618–1624

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Yamashita Y, Bowen WH, Burne RA et al (1993) Role of the Streptococcus mutans gtf genes in caries induction in the specific-pathogen-free rat model. Infect Immun 61:3811–3817

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Zhang L, Foxman B, Drake DR et al (2009) Comparative whole-genome analysis of Streptococcus mutans isolates within and among individuals of different caries status. Oral Microbiol Immunol 24:197–203. doi:10.1111/j.1399-302X.2008.00495.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was supported by funding from Peking University School of Stomatology (PKUSS20130210).

Author information

Authors and Affiliations

  1. Central Laboratory, Peking University School and Hospital of Stomatology, No. 22, Zhongguancun South Avenue, Haidian District, Beijing, 100081, People’s Republic of China

    Peiqi Meng, Qian Zhang & Feng Chen

  2. Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, People’s Republic of China

    Peiqi Meng & Jiuxiang Lin

  3. Department of Periodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, People’s Republic of China

    Chang Lu

Authors
  1. Peiqi Meng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chang Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiuxiang Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Feng Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Feng Chen.

Ethics declarations

Conflicts of interest

None.

Electronic Supplementary Material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Meng, P., Lu, C., Zhang, Q. et al. Exploring the Genomic Diversity and Cariogenic Differences of Streptococcus mutans Strains Through Pan-Genome and Comparative Genome Analysis. Curr Microbiol 74, 1200–1209 (2017). https://doi.org/10.1007/s00284-017-1305-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00284-017-1305-z

Search

Navigation