Virus Genes

, Volume 55, Issue 3, pp 381–393 | Cite as

A novel phage from periodontal pockets associated with chronic periodontitis

  • Yu Zhang
  • Tong-Ling ShanEmail author
  • Fei Li
  • Tian Yu
  • Xi Chen
  • Xu-Tao Deng
  • Eric Delwart
  • Xi-Ping FengEmail author


Bacteriophages often constitute the majority of periodontal viral communities, but phages that infect oral bacteria remain uncharacterized. Here, we present the genetic analysis of the genome of a novel siphovirus, named Siphoviridae_29632, which was isolated from a patient with periodontitis using a viral metagenomics-based approach. Among 43 predicted open reading frames (ORFs) in the genome, the viral genes encoding structural proteins were distinct from the counterparts of other viruses, although a distant homology is shared among viral morphogenesis proteins. A total of 28 predicted coding sequences had significant homology to other known phage ORF sequences. In addition, the prevalence of Siphoviridae_29632 in a cohort of patients with chronic periodontitis was 41.67%, which was significantly higher than that in the healthy group (4.55%, P < 0.001), suggesting that this virus as well as its hosts may contribute to the ecological environment favored for chronic periodontitis.


Bacteriophage Siphovirus Periodontitis Viral metagenomics Case–control study 



The authors are grateful to all participates in the research and appreciate the efforts of teams in the Department of Swine Infectious Disease, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.

Author contributions

XPF and TLS designed the study. XTD and ED completed the data analysis and statistics. YZ and FL completed the sample collection and the amplifications of the newly discovered full-length human anellovirus. YZ, TY, and XC completed the epidemiological investigation. All of the authors have read and approved the final manuscript.


The study was funded by the National Natural Science Foundation of China (Nos. 81800967 and 81470737).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Ethics Committee of the Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University approved this study (No. 201406).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11262_2019_1658_MOESM1_ESM.docx (1.6 mb)
Supplementary material 1 (DOCX 1612 kb)
11262_2019_1658_MOESM2_ESM.docx (18 kb)
Supplementary material 2 (DOCX 17 kb)


  1. 1.
    Solbiati J, Frias-Lopez J (2018) Metatranscriptome of the oral microbiome in health and disease. J Dent Res 97(5):492–500. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Eke PI, Dye BA, Wei L, Thornton-Evans GO, Genco RJ (2012) Prevalence of periodontitis in adults in the United States: 2009 and 2010. J Dent Res 91(10):914–920. CrossRefPubMedGoogle Scholar
  3. 3.
    Al-Rasheed A, Scheerens H, Rennick DM, Fletcher HM, Tatakis DN (2003) Accelerated alveolar bone loss in mice lacking interleukin-10. J Dent Res 82(8):632–635. CrossRefPubMedGoogle Scholar
  4. 4.
    Assuma R, Oates T, Cochran D, Amar S, Graves DT (1998) IL-1 and TNF antagonists inhibit the inflammatory response and bone loss in experimental periodontitis. J Immunol 160(1):403–409PubMedGoogle Scholar
  5. 5.
    Ly M, Abeles SR, Boehm TK, Robles-Sikisaka R, Naidu M, Santiago-Rodriguez T, Pride DT (2014) Altered oral viral ecology in association with periodontal disease. mBio 5(3):01133. CrossRefGoogle Scholar
  6. 6.
    Pride DT, Salzman J, Haynes M, Rohwer F, Davis-Long C, White RA 3rd, Loomer P, Armitage GC, Relman DA (2012) Evidence of a robust resident bacteriophage population revealed through analysis of the human salivary virome. ISME J 6(5):915–926. CrossRefPubMedGoogle Scholar
  7. 7.
    Willner D, Furlan M, Schmieder R, Grasis JA, Pride DT, Relman DA, Angly FE, McDole T, Mariella RP Jr, Rohwer F, Haynes M (2011) Metagenomic detection of phage-encoded platelet-binding factors in the human oral cavity. Proc Natl Acad Sci USA 108(Suppl 1):4547–4553. CrossRefPubMedGoogle Scholar
  8. 8.
    Robles-Sikisaka R, Ly M, Boehm T, Naidu M, Salzman J, Pride DT (2013) Association between living environment and human oral viral ecology. ISME J 7(9):1710–1724. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Minot S, Bryson A, Chehoud C, Wu GD, Lewis JD, Bushman FD (2013) Rapid evolution of the human gut virome. Proc Natl Acad Sci USA 110(30):12450–12455. CrossRefPubMedGoogle Scholar
  10. 10.
    Breitbart M, Hewson I, Felts B, Mahaffy JM, Nulton J, Salamon P, Rohwer F (2003) Metagenomic analyses of an uncultured viral community from human feces. J Bacteriol 185(20):6220–6223CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Sullivan MB, Waterbury JB, Chisholm SW (2003) Cyanophages infecting the oceanic cyanobacterium Prochlorococcus. Nature 424(6952):1047–1051. CrossRefPubMedGoogle Scholar
  12. 12.
    Wichels A, Biel SS, Gelderblom HR, Brinkhoff T, Muyzer G, Schutt C (1998) Bacteriophage diversity in the North Sea. Appl Environ Microbiol 64(11):4128–4133PubMedPubMedCentralGoogle Scholar
  13. 13.
    Pinto G, Silva MD, Peddey M, Sillankorva S, Azeredo J (2016) The role of bacteriophages in periodontal health and disease. Future Microbiol 11:1359–1369. CrossRefPubMedGoogle Scholar
  14. 14.
    Al-Jarbou AN (2012) Genomic library screening for viruses from the human dental plaque revealed pathogen-specific lytic phage sequences. Curr Microbiol 64(1):1–6. CrossRefPubMedGoogle Scholar
  15. 15.
    Duerkop BA, Clements CV, Rollins D, Rodrigues JL, Hooper LV (2012) A composite bacteriophage alters colonization by an intestinal commensal bacterium. Proc Natl Acad Sci USA 109(43):17621–17626. CrossRefPubMedGoogle Scholar
  16. 16.
    Allen HK, Looft T, Bayles DO, Humphrey S, Levine UY, Alt D, Stanton TB (2011) Antibiotics in feed induce prophages in swine fecal microbiomes. mBio 2(6):e00260. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Parada V, Baudoux AC, Sintes E, Weinbauer MG, Herndl GJ (2008) Dynamics and diversity of newly produced virioplankton in the North Sea. ISME J 2(9):924–936. CrossRefPubMedGoogle Scholar
  18. 18.
    Rodriguez-Brito B, Li L, Wegley L, Furlan M, Angly F, Breitbart M, Buchanan J, Desnues C, Dinsdale E, Edwards R, Felts B, Haynes M, Liu H, Lipson D, Mahaffy J, Martin-Cuadrado AB, Mira A, Nulton J, Pasic L, Rayhawk S, Rodriguez-Mueller J, Rodriguez-Valera F, Salamon P, Srinagesh S, Thingstad TF, Tran T, Thurber RV, Willner D, Youle M, Rohwer F (2010) Viral and microbial community dynamics in four aquatic environments. ISME J 4(6):739–751. CrossRefPubMedGoogle Scholar
  19. 19.
    Rodriguez-Valera F, Martin-Cuadrado AB, Rodriguez-Brito B, Pasic L, Thingstad TF, Rohwer F, Mira A (2009) Explaining microbial population genomics through phage predation. Nat Rev Microbiol 7(11):828–836. CrossRefPubMedGoogle Scholar
  20. 20.
    Sandaa RA, Gomez-Consarnau L, Pinhassi J, Riemann L, Malits A, Weinbauer MG, Gasol JM, Thingstad TF (2009) Viral control of bacterial biodiversity–evidence from a nutrient-enriched marine mesocosm experiment. Environ Microbiol 11(10):2585–2597. CrossRefPubMedGoogle Scholar
  21. 21.
    Paisano AF, Spira B, Cai S, Bombana AC (2004) In vitro antimicrobial effect of bacteriophages on human dentin infected with Enterococcus faecalis ATCC 29212. Oral Microbiol Immunol 19(5):327–330. CrossRefPubMedGoogle Scholar
  22. 22.
    Aljarbou AN, Aljofan M (2014) Genotyping, morphology and molecular characteristics of a lytic phage of Neisseria strain obtained from infected human dental plaque. J Microbiol 52(7):609–618. CrossRefPubMedGoogle Scholar
  23. 23.
    Bachrach G, Leizerovici-Zigmond M, Zlotkin A, Naor R, Steinberg D (2003) Bacteriophage isolation from human saliva. Lett Appl Microbiol 36(1):50–53CrossRefPubMedGoogle Scholar
  24. 24.
    Delisle AL, Nauman RK, Minah GE (1978) Isolation of a bacteriophage for actinomyces viscosus. Infect Immunity 20(1):303–306Google Scholar
  25. 25.
    Farrar MD, Howson KM, Bojar RA, West D, Towler JC, Parry J, Pelton K, Holland KT (2007) Genome sequence and analysis of a Propionibacterium acnes bacteriophage. J Bacteriol 189(11):4161–4167. CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Haubek D, Willi K, Poulsen K, Meyer J, Kilian M (1997) Presence of bacteriophage Aa phi 23 correlates with the population genetic structure of Actinobacillus actinomycetemcomitans. Eur J Oral Sci 105(1):2–8CrossRefPubMedGoogle Scholar
  27. 27.
    Zhan Y, Huang S, Voget S, Simon M, Chen F (2016) A novel roseobacter phage possesses features of podoviruses, siphoviruses, prophages and gene transfer agents. Sci Rep 6:30372. CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Edlund A, Santiago-Rodriguez TM, Boehm TK, Pride DT (2015) Bacteriophage and their potential roles in the human oral cavity. J Oral Microbiol 7:27423. CrossRefPubMedGoogle Scholar
  29. 29.
    Hitch G, Pratten J, Taylor PW (2004) Isolation of bacteriophages from the oral cavity. Lett Appl Microbiol 39(2):215–219. CrossRefPubMedGoogle Scholar
  30. 30.
    Allander T, Emerson SU, Engle RE, Purcell RH, Bukh J (2001) A virus discovery method incorporating DNase treatment and its application to the identification of two bovine parvovirus species. Proc Natl Acad Sci USA 98(20):11609–11614. CrossRefPubMedGoogle Scholar
  31. 31.
    Zhang Y, Li F, Shan TL, Deng X, Delwart E, Feng XP (2016) A novel species of torque teno mini virus (TTMV) in gingival tissue from chronic periodontitis patients. Sci Rep 6:26739. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Zhang Y, Li F, Chen X, Shan TL, Deng XT, Delwart E, Feng XP (2017) Detection of a new species of torque teno mini virus from the gingival epithelium of patients with periodontitis. Virus Genes 53(6):823–830. CrossRefPubMedGoogle Scholar
  33. 33.
    Zhang W, Yang S, Shan T, Hou R, Liu Z, Li W, Guo L, Wang Y, Chen P, Wang X, Feng F, Wang H, Chen C, Shen Q, Zhou C, Hua X, Cui L, Deng X, Zhang Z, Qi D, Delwart E (2017) Virome comparisons in wild-diseased and healthy captive giant pandas. Microbiome 5(1):90. CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Phan TG, Kapusinszky B, Wang C, Rose RK, Lipton HL, Delwart EL (2011) The fecal viral flora of wild rodents. PLoS Pathog 7(9):e1002218. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4(4):406–425. CrossRefPubMedGoogle Scholar
  36. 36.
    Brum JR, Ignacio-Espinoza JC, Roux S, Doulcier G, Acinas SG, Alberti A, Chaffron S, Cruaud C, de Vargas C, Gasol JM, Gorsky G, Gregory AC, Guidi L, Hingamp P, Iudicone D, Not F, Ogata H, Pesant S, Poulos BT, Schwenck SM, Speich S, Dimier C, Kandels-Lewis S, Picheral M, Searson S, Tara Oceans C, Bork P, Bowler C, Sunagawa S, Wincker P, Karsenti E, Sullivan MB (2015) Ocean plankton Patterns and ecological drivers of ocean viral communities. Science 348(6237):1261498. CrossRefPubMedGoogle Scholar
  37. 37.
    Vage S, Storesund JE, Thingstad TF (2013) SAR11 viruses and defensive host strains. Nature 499(7459):E3–4. CrossRefPubMedGoogle Scholar
  38. 38.
    Katsura I (1987) Determination of bacteriophage lambda tail length by a protein ruler. Nature 327(6117):73–75. CrossRefPubMedGoogle Scholar
  39. 39.
    Pedersen M, Ostergaard S, Bresciani J, Vogensen FK (2000) Mutational analysis of two structural genes of the temperate lactococcal bacteriophage TP901-1 involved in tail length determination and baseplate assembly. Virology 276(2):315–328. CrossRefPubMedGoogle Scholar
  40. 40.
    Stevens RH, Preus HR, Dokko B, Russell DT, Furgang D, Schreiner HC, Goncharoff P, Figurski DH, Fine DH (1994) Prevalence and distribution of bacteriophage phi Aa DNA in strains of Actinobacillus actinomycetemcomitans. FEMS Microbiol Lett 119(3):329–337PubMedGoogle Scholar
  41. 41.
    Tylenda CA, Calvert C, Kolenbrander PE, Tylenda A (1985) Isolation of Actinomyces bacteriophage from human dental plaque. Infect immunity 49(1):1–6Google Scholar
  42. 42.
    Olsen I, Namork E, Myhrvold V (1993) Electron microscopy of phages in serotypes of Actinobacillus actinomycetemcomitans. Oral Microbiol Immunol 8(6):383–385CrossRefPubMedGoogle Scholar
  43. 43.
    Preus HR, Olsen I, Gjermo P (1987) Bacteriophage infection—a possible mechanism for increased virulence of bacteria associated with rapidly destructive periodontitis. Acta Odontol Scand 45(1):49–54CrossRefPubMedGoogle Scholar
  44. 44.
    Willi K, Sandmeier H, Asikainen S, Saarela M, Meyer J (1997) Occurrence of temperate bacteriophages in different Actinobacillus actinomycetemcomitans serotypes isolated from periodontally healthy individuals. Oral Microbiol Immunol 12(1):40–46CrossRefPubMedGoogle Scholar
  45. 45.
    Abeles SR, Robles-Sikisaka R, Ly M, Lum AG, Salzman J, Boehm TK, Pride DT (2014) Human oral viruses are personal, persistent and gender-consistent. ISME J 8(9):1753–1767. CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Poullain V, Gandon S, Brockhurst MA, Buckling A, Hochberg ME (2008) The evolution of specificity in evolving and coevolving antagonistic interactions between a bacteria and its phage. Evol Int J Org Evol 62(1):1–11. CrossRefGoogle Scholar
  47. 47.
    Lee S, Ward TJ, Siletzky RM, Kathariou S (2012) Two novel type II restriction-modification systems occupying genomically equivalent locations on the chromosomes of Listeria monocytogenes strains. Appl Environ Microbiol 78(8):2623–2630. CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Pride DT, Meinersmann RJ, Wassenaar TM, Blaser MJ (2003) Evolutionary implications of microbial genome tetranucleotide frequency biases. Genome Res 13(2):145–158. CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Shibata Y, Yamashita Y, van der Ploeg JR (2009) The serotype-specific glucose side chain of rhamnose-glucose polysaccharides is essential for adsorption of bacteriophage M102 to Streptococcus mutans. FEMS Microbiol Lett 294(1):68–73. CrossRefPubMedGoogle Scholar
  50. 50.
    Szafranski SP, Winkel A, Stiesch M (2017) The use of bacteriophages to biocontrol oral biofilms. J Biotechnol 250:29–44. CrossRefPubMedGoogle Scholar
  51. 51.
    Machuca P, Daille L, Vines E, Berrocal L, Bittner M (2010) Isolation of a novel bacteriophage specific for the periodontal pathogen Fusobacterium nucleatum. Appl Environ Microbiol 76(21):7243–7250. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Yu Zhang
    • 1
    • 3
  • Tong-Ling Shan
    • 2
    • 4
    Email author
  • Fei Li
    • 1
    • 3
  • Tian Yu
    • 1
    • 3
  • Xi Chen
    • 1
    • 3
  • Xu-Tao Deng
    • 5
    • 6
  • Eric Delwart
    • 5
    • 6
  • Xi-Ping Feng
    • 1
    • 3
    Email author
  1. 1.Department of Preventive Dentistry, Ninth People’s HospitalShanghai JiaoTong University School of MedicineShanghaiChina
  2. 2.Department of Swine Infectious Disease, Shanghai Veterinary Research InstituteChinese Academy of Agricultural SciencesShanghaiChina
  3. 3.Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of StomatologyNational Clinical Research Center of StomatologyShanghaiChina
  4. 4.Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and ZoonosesYangzhouChina
  5. 5.Blood Systems Research InstituteSan FranciscoUSA
  6. 6.Department of Laboratory MedicineUniversity of California at San FranciscoSan FranciscoUSA

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