Ureaplasma urealyticum causes hyperammonemia in an experimental immunocompromised murine model

Xiaohui Wang, Melissa J. Karau, Kerryl E. Greenwood-Quaintance, Darci R. Block, Jayawant Mandrekar, Scott A. Cunningham, Robin Patel

Research output: Contribution to journalArticle

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Abstract

Hyperammonemia syndrome is an often fatal complication of lung transplantation which has been recently associated with Ureaplasma infection. It has not been definitely established that Ureaplasma species can cause hyperammonemia. We established a novel immunocompromised murine model of Ureaplasma urealyticum infection and used it to confirm that U. urealyticum can cause hyperammonemia. Male C3H mice were pharmacologically immunosuppressed with mycophenolate mofetil, tacrolimus and oral prednisone for seven days, and then challenged intratracheally (IT) and/or intraperitoneally (IP) with 107 CFU U. urealyticum over six days, while continuing immunosuppression. Spent U. urealyticum- free U9 broth was used as a negative control, with uninfected immunocompetent mice, uninfected immunosuppressed mice, and infected immunocompetent mice serving as additional controls. Plasma ammonia concentrations were compared using Wilcoxon ranks sum tests. Plasma ammonia concentrations of immunosuppressed mice challenged IT/IP with spent U9 broth (n = 14) (range 155-330 μmol/L) were similar to those of normal mice (n = 5), uninfected immunosuppressed mice (n = 5), and U. urealyticum IT/IP challenged immunocompetent mice (n = 5) [range 99-340 μmol/L, p = 0.60]. However, immunosuppressed mice challenged with U. urealyticum IT/IP (n = 20) or IP (n = 15) had higher plasma ammonia concentrations (range 225-945 μmol/L and 276-687 μmol/L, respectively) than those challenged IT/IP with spent U9 broth (p<0.001). U. urealyticum administered IT/IP or IP causes hyperammonemia in mice pharmacologically immunosuppressed with a regimen similar to that administered to lung transplant recipients.

Original languageEnglish (US)
Article numbere0161214
JournalPLoS One
Volume11
Issue number8
DOIs
StatePublished - Aug 1 2016

Fingerprint

Ureaplasma urealyticum
Hyperammonemia
Ammonia
animal models
Plasmas
mice
Mycophenolic Acid
Transplants
Ureaplasma Infections
Tacrolimus
Prednisone
Ureaplasma
ammonia
Nonparametric Statistics
lungs
tacrolimus
Lung Transplantation
prednisone
Inbred C3H Mouse
immunosuppression

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Wang, X., Karau, M. J., Greenwood-Quaintance, K. E., Block, D. R., Mandrekar, J., Cunningham, S. A., & Patel, R. (2016). Ureaplasma urealyticum causes hyperammonemia in an experimental immunocompromised murine model. PLoS One, 11(8), [e0161214]. https://doi.org/10.1371/journal.pone.0161214

Ureaplasma urealyticum causes hyperammonemia in an experimental immunocompromised murine model. / Wang, Xiaohui; Karau, Melissa J.; Greenwood-Quaintance, Kerryl E.; Block, Darci R.; Mandrekar, Jayawant; Cunningham, Scott A.; Patel, Robin.

In: PLoS One, Vol. 11, No. 8, e0161214, 01.08.2016.

Research output: Contribution to journalArticle

Wang X, Karau MJ, Greenwood-Quaintance KE, Block DR, Mandrekar J, Cunningham SA et al. Ureaplasma urealyticum causes hyperammonemia in an experimental immunocompromised murine model. PLoS One. 2016 Aug 1;11(8). e0161214. https://doi.org/10.1371/journal.pone.0161214
Wang, Xiaohui ; Karau, Melissa J. ; Greenwood-Quaintance, Kerryl E. ; Block, Darci R. ; Mandrekar, Jayawant ; Cunningham, Scott A. ; Patel, Robin. / Ureaplasma urealyticum causes hyperammonemia in an experimental immunocompromised murine model. In: PLoS One. 2016 ; Vol. 11, No. 8.
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