Skip to main content

Differences in mortality in Fusobacterium necrophorum and Fusobacterium nucleatum infections detected by culture and 16S rRNA gene sequencing

European Journal of Clinical Microbiology & Infectious Diseases volume 38, pages 75–80 (2019)Cite this article

Abstract

Fusobacterium species are components of the normal microbiota of the oral cavity, gastrointestinal tract, and female genital tract. They are increasingly recognized as causative agents of oral, laryngeal, and tonsillar infections. Several fusobacterial species are involved in infections, with F. necrophorum and F. nucleatum being the most commonly cultured subtypes. In this study, we aimed to investigate clinical and prognostic differences in terms of mortality and association with malignancy between F. necrophorum and F. nucleatum detected by culture and 16S rRNA gene sequencing. This is a systematic, comparative, retrospective, non-interventional study. Data were extracted from the Department of Clinical Microbiology, Region Zealand, Denmark: all patients with F. necrophorum or F. nucleatum detected by culture or 16S rRNA gene sequencing from 1st of January 2010 to 30th of June 2015 were included. In total, F. necrophorum was detected in samples from 75 patients, and F. nucleatum in samples from 68 patients (total: n = 143). Thirteen patients had a current cancer diagnosis at the time of fusobacterial sampling. Multivariate analyses revealed a significant association of “current cancer” with 30-day mortality. Fusobacterial subtype was not associated with mortality neither in overall nor in subgroups with or without current cancer. Despite differences in clinical disease pattern between F. necrophorum and F. nucleatum, mortality was unaffected by fusobacterial subtype. Mortality was significantly related to comorbidity, especially a current diagnosis of cancer. Our data highlights the current debate whether fusobacterial involvement in cancer may have disease-altering properties, rather than being opportunistic pathogens secondary to cancer disease.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

References

  1. Han YW (2015) Fusobacterium nucleatum: a commensal-turned pathogen. Curr Opin Microbiol 23:141–147

    Article  CAS  PubMed  Google Scholar 

  2. Bank S, Jensen A, Nielsen HM, Kristensen LH, Voldstedlund M, Prag J (2016) Fusobacterium necrophorum findings in Denmark from 2010 to 2014 using data from the Danish microbiology database. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 124(12):1087–1092

    Article  PubMed  Google Scholar 

  3. Holm K, Bank S, Nielsen H, Kristensen LH, Prag J, Jensen A (2016) The role of Fusobacterium necrophorum in pharyngotonsillitis - a review. Anaerobe 42:89–97

    Article  CAS  PubMed  Google Scholar 

  4. Huggan PJ, Murdoch DR (2008) Fusobacterial infections: clinical spectrum and incidence of invasive disease. J Infect 57(4):283–289

    Article  PubMed  Google Scholar 

  5. Johannesen K, Dessau R, Heltberg O, Bodtger U (2016) Bad news itself or just the messenger? The high mortality of Fusobacterium spp. infections is related to disseminated malignancy and other comorbidities. Eur Clin Respir J 3:30287

    Article  PubMed  Google Scholar 

  6. Ehlers Klug T, Rusan M, Fuursted K, Ovesen T (2009) Fusobacterium necrophorum: most prevalent pathogen in peritonsillar abscess in Denmark. Clin Infect Dis 49(10):1467–1472

    Article  PubMed  Google Scholar 

  7. Johannesen K, Bodtger U, Heltberg O (2014) Lemierre’s syndrome: the forgotten disease. J Thromb Thrombolysis 37(3):246–248

    Article  PubMed  Google Scholar 

  8. Rubinstein MR, Wang X, Liu W, Hao Y, Cai G, Han YW (2013) Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/beta-catenin signaling via its FadA adhesin. Cell Host Microbe 14(2):195–206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Patel M (2013) 16S rDNA PCR in diagnosis of Lemierre’s syndrome. Lancet Infect Dis 13(3):197

    Article  CAS  PubMed  Google Scholar 

  10. Gleesen AS, Grarup C, Dargis R, Andresen K, Christensen JJ, Kemp M (2008) PCR and DNA sequencing in establishing the aetiology of bacterial infections in children. APMIS: acta pathologica, microbiologica, et immunologica Scandinavica 116(9):811–815

    Article  CAS  PubMed  Google Scholar 

  11. Mitsuhashi K, Nosho K, Sukawa Y, Matsunaga Y, Ito M, Kurihara H et al (2015) Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis. Oncotarget 6(9):7209–7220

    Article  PubMed  PubMed Central  Google Scholar 

  12. Castellarin M, Warren RL, Freeman JD, Dreolini L, Krzywinski M, Strauss J et al (2012) Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res 22(2):299–306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kostic AD, Gevers D, Pedamallu CS, Michaud M, Duke F, Earl AM et al (2012) Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res 22(2):292–298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. McCoy AN, Araujo-Perez F, Azcarate-Peril A, Yeh JJ, Sandler RS, Keku TO (2013) Fusobacterium is associated with colorectal adenomas. PLoS One 8(1):e53653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Flanagan L, Schmid J, Ebert M, Soucek P, Kunicka T, Liska V et al (2014) Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome. Eur J Clin Microbiol Infect Dis 33(8):1381–1390

    Article  CAS  PubMed  Google Scholar 

  16. Abed J, Maalouf N, Parhi L, Chaushu S, Mandelboim O, Bachrach G (2017) Tumor targeting by Fusobacterium nucleatum: a pilot study and future perspectives. Front Cell Infect Microbiol 7:295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kostic AD, Chun E, Robertson L, Glickman JN, Gallini CA, Michaud M et al (2013) Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 14(2):207–215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Nosho K, Sukawa Y, Adachi Y, Ito M, Mitsuhashi K, Kurihara H et al (2016) Association of Fusobacterium nucleatum with immunity and molecular alterations in colorectal cancer. World J Gastroenterol 22(2):557–566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ahn J, Sinha R, Pei Z, Dominianni C, Wu J, Shi J et al (2013) Human gut microbiome and risk for colorectal cancer. J Natl Cancer Inst 105(24):1907–1911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors wish to thank Jørgen Harald Engberg for his revision of the manuscript.

Contributions

KJ analyzed data and drafted the manuscript; SK provided data, did lab work, and revised the manuscript; NG compiled all data and revised the manuscript; XN did lab work and wrote part of the methods section as well as revised the manuscript; TB conceptualized the manuscript and revised it and UB conceptualized the manuscript, analyzed data, and revised the manuscript.

Author information

Authors and Affiliations

  1. Department of Respiratory Medicine, Næstved Hospital, 61 Ringstedgade, DK-4700, Næstved, Denmark

    Katrine M. Johannesen & Uffe Bodtger

  2. Department of Respiratory and Internal Medicine, Zealand University Hospital Roskilde, Roskilde, Denmark

    Shailesh B. Kolekar, Nikolaos Greve, Toke Seierøe Barfod & Uffe Bodtger

  3. Department of Clinical Microbiology, Slagelse Hospital, Slagelse, Denmark

    Xiaohui Chen Nielsen

  4. Institute for Regional Health Research, University of Southern Denmark, Odense, Denmark

    Uffe Bodtger

Authors
  1. Katrine M. Johannesen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shailesh B. Kolekar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nikolaos Greve
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaohui Chen Nielsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Toke Seierøe Barfod
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Uffe Bodtger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Uffe Bodtger.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest to report.

Access to data

Access to data will be granted by request to those eligible for this.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Johannesen, K.M., Kolekar, S.B., Greve, N. et al. Differences in mortality in Fusobacterium necrophorum and Fusobacterium nucleatum infections detected by culture and 16S rRNA gene sequencing. Eur J Clin Microbiol Infect Dis 38, 75–80 (2019). https://doi.org/10.1007/s10096-018-3394-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-018-3394-4

Keywords

  • Fusobacteria
  • F. necrophorum
  • F. nucleatum
  • Infections
  • Mortality