Case Report | Published:

Identification of Burkholderia fungorum in the urine of an individual with spinal cord injury and augmentation cystoplasty using 16S sequencing: copathogen or innocent bystander?

Spinal Cord Series and Casesvolume 4, Article number: 85 (2018) | Download Citation

Abstract

Introduction

People with neuropathic bladder (NB) secondary to spinal cord injury (SCI) are at risk for multiple genitourinary complications, the most frequent of which is urinary tract infection (UTI). Despite the high frequency with which UTI occurs, our understanding of the role of urinary microbes in health and disease is limited. In this paper, we present the first prospective case study integrating symptom reporting, urinalysis, urine cultivation, and 16S ribosomal ribonucleic acid (rRNA) sequencing of the urine microbiome.

Case presentation

A 55-year-old male with NB secondary to SCI contributed 12 urine samples over an 8-month period during asymptomatic, symptomatic, and postantibiotic periods. All bacteria identified on culture were present on 16S rRNA sequencing, however, 16S rRNA sequencing revealed the presence of bacteria not isolated on culture. In particular, Burkholderia fungorum was present in three samples during both asymptomatic and symptomatic periods. White blood cells of ≥5–10/high power field and leukocyte esterase ≥2 on urinalysis was associated with the presence of symptoms.

Discussion

In this patient, there was a predominance of pathogenic bacteria and a lack of putative probiotic bacteria during both symptomatic and asymptomatic states. Urinalysis-defined inflammatory markers were present to a greater extent during symptomatic periods compared to the asymptomatic state, which may underscore a role for urinalysis or other inflammatory markers in differentiating asymptomatic bacteriuria from UTI in patients with NB. The finding of potentially pathogenic bacteria identified by sequencing but not cultivation, suggests a need for greater understanding of the relationships amongst bacterial species in the bacteriuric neuropathic bladder.

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References

  1. 1.

    Litza JA, Brill JR. Urinary tract infections. Prim Care. 2010;37:491–507.

  2. 2.

    Cardenas DD, Hoffman JM, Kirshblum S, McKinley W. Etiology and incidence of rehospitalization after traumatic spinal cord injury: a multicenter analysis. Arch Phys Med Rehabil. 2004;85:1757–63.

  3. 3.

    Chen Y, DeVivo MJ, Roseman JM. Current trend and risk factors for kidney stones in persons with spinal cord injury: a longitudinal study. Spinal Cord. 2000;38:346–53.

  4. 4.

    Hansen RB, Biering-Sørensen F, Kristensen JK. Urinary calculi following traumatic spinal cord injury. Scand J Urol Nephrol. 2007;41:115–9.

  5. 5.

    Groah SL, Weitzenkamp DA, Lammertse DP, Whiteneck GG, Lezotte DC, Hamman RF. Excess risk of bladder cancer in spinal cord injury: evidence for an association between indwelling catheter use and bladder cancer. Arch Phys Med Rehabil. 2002;83:346–51.

  6. 6.

    Groah SL, Lammertse DP. Factors associated with survival after bladder cancer in spinal cord injury. J Spinal Cord Med. 2003;26:339–44.

  7. 7.

    Cardenas DD, Moore KN, Dannels-McClure A, Scelza WM, Graves DE, Brooks M, et al. Intermittent catheterization with a hydrophilic-coated catheter delays urinary tract infections in acute spinal cord injury: a prospective, randomized, multicenter trial. PM&R. 2011;3:408–17.

  8. 8.

    Haisma JA, van der Woude LH, Stam HJ, Bergen MP, Sluis TA, Post MW, et al. Complications following spinal cord injury: occurrence and risk factors in a longitudinal study during and after inpatient rehabilitation. J Rehabil Med. 2007;39:393–8.

  9. 9.

    Esclarín De Ruz A, García Leoni E, Herruzo Cabrera R. Epidemiology and risk factors for urinary tract infection in patients with spinal cord injury. J Urol. 2000;164:1285–9.

  10. 10.

    Ronald A. The etiology of urinary tract infection: traditional and emerging pathogens. Am J Med. 2002;113(Suppl 1A):14S–9S.

  11. 11.

    Ottolini MC, Shaer CM, Rushton HG, Majd M, Gonzales EC, Patel KM. Relationship of asymptomatic bacteriuria and renal scarring in children with neuropathic bladders who are practicing clean intermittent catheterization. J Pediatr. 1995;127:368–72.

  12. 12.

    Fouts D, Pieper R, Szpakowski S, Pohl H, Knoblach S, Suh M, et al. Integrated next-generation sequencing of 16S rDNA and metaproteomics differentiate the healthy urine microbiome from asymptomatic bacteriuria in neuropathic bladder associated with spinal cord injury. J Transl Med. 2012:174.

  13. 13.

    Groah S, Pérez-Losada M, Caldovic L, Ljungberg I, Sprague B, Castro-Nallar E, et al. Redefining Healthy Urin: A Cross-Sect Explor Metagenomic Study People Bladder Dysfunct. 2016;196:579–87.

  14. 14.

    Hooton T, Bradley S, Cardenas D, Colgan R, Geerlings S, Rice J, et al. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 2010;50:625–63.

  15. 15.

    Vigil H, Hickling D. Urinary tract infection in the neurogenic bladder. Transl Androl Urol. 2016;5:72–87.

  16. 16.

    Coenye T, Laevens S, Willems A, Ohlén M, Hannant W, Govan J, et al. Burkholderia fungorum sp. nov. and Burkholderia caledonica sp. nov., two new species isolated from the environment, animals and human clinical samples. Int J Syst Evolut Microbiol. 2001;51(Pt 3):1099–107.

  17. 17.

    Coenye T, Goris J, Spilker T, Vandamme P, Lipula J. Characterization of unusual bacteria isolated from respiratory secretions of cystic fibrosis patients and description of Inquilinus limosus gen. nov., so. nov. J Clin Microbiol. 2002;40:2062–9.

  18. 18.

    Oberbach A, Schlichting N, Feder S, Lehmann S, Kullnick Y, Buschmann T. et al. New insights into valve-related intramural and intracellular bacterial diversity in infective endocarditis. Public Libr Sci. 2017;12:e0175569.

  19. 19.

    Qing Xia, Cheng L, Zhang H, Sun S, Liu F, Jing H, et al. Identification of Vaginal Bacteria Diversity and its Association with clinically diagnosed bacterial vaginosis by denaturing gradient gel electrophoresis and correspondence analysis. Infect Genet Evol. 2016;44:479–86.

  20. 20.

    Yang L, Poles M, Fisch G, Ma Y, Nossa C, Phelan J, et al. HIV-induced immunosuppression is associated with colonization of the proximal gut by environmental bacteria. AIDS 2016;30:19–29.

  21. 21.

    Gerritis P, Klaassen C, Coenye T, Vandamme P, Meis JF. Burkholderia fungorum septicemia. Emerg Infect Dis. 2005;11:1115–7.

  22. 22.

    Loon S, SOh Y, Mahfodz N, Johari J, AbuBakar S. Synovial tissue infection with Burkholderia fungorum. Emerg Infect Dis. 2016;22:1834–5.

  23. 23.

    Zhang R, Ran Y, Dai Y, Zhang H, Lu Y, Wang L. Infectious granuloma caused by Burkholderia fungorum confirmed by laser-capture microdissection and polymerase chain reaction. Br J Dermatol. 2014;1:1261–2.

  24. 24.

    Heath R, Cockerell C, Mankoo R, Ibdah J, Tahan V.Fecal microbiota transplantation and its potential the rapeutic uses in gastrointestinal disorders.North Clin Istanb. 2018;5:79–88.

  25. 25.

    University of Pennsylvania School of Medicine. Potential of manipulating gut microbiome to boost efficacy of cancer immunotherapies. ScienceDaily. www.sciencedaily.com/releases/2018/04/180402171038.htm. Accessed 8 April 2018.

  26. 26.

    Goldenberg J, Yap C, Lytvyn L, Lo C, Beardsley J, Mertz D. et al. Probiotics for Prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Libr. 2017;12:CD006095 https://doi.org/10.1002/14651858.CD006095.pub4.

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Author information

Affiliations

  1. MedStar National Rehabilitation Hospital, 102 Irving St., NW, Washington, DC, 20010, USA

    • Emma Nally
    • , Suzanne L. Groah
    •  & Inger Ljungberg
  2. Department of Rehabilitation Medicine, MedStar Georgetown University Hospital, Washington, DC, USA

    • Emma Nally
    •  & Suzanne L. Groah
  3. Computational Biology Institute, The George Washington University, Ashburn, VA, USA

    • Marcos Pérez-Losada
  4. Department of Integrative Systems Biology, Children’s National Health System, Washington, DC, USA

    • Marcos Pérez-Losada
    •  & Ljubica Caldovic
  5. CIBIO-InBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, , Universidade do Porto, 4485-661, Vairão, Porto, Portugal

    • Marcos Pérez-Losada
  6. Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY, USA

    • Neel J. Chandel
  7. Division of Urology, Children’s National Health System, Washington, DC, USA

    • Bruce Sprague
    • , Michael H. Hsieh
    •  & Hans G. Pohl

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Conflict of interest

The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Suzanne L. Groah.

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DOI

https://doi.org/10.1038/s41394-018-0115-2