title: Ureaplasma urealyticum Causes Hyperammonemia in an Experimental Immunocompromised Murine Model.
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.
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Karau
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Kerryl E
authors.initials: KE
authors.lastname: Greenwood-Quaintance
authors.affiliation: Division of Clinical Core Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Darci R
authors.initials: DR
authors.lastname: Block
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Jayawant N
authors.initials: JN
authors.lastname: Mandrekar
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Cunningham
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America.|Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Robin
authors.identifier: http://orcid.org/0000-0001-6344-4141
authors.initials: R
authors.lastname: Patel
mesh_terms: D000641:Ammonia / Q000097:blood; D000818:Animals; D004195:Disease Models, Animal; D022124:Hyperammonemia / Q000209:etiology*; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009173:Mycophenolic Acid / Q000494:pharmacology; D011241:Prednisone / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D016559:Tacrolimus / Q000494:pharmacology; D016869:Ureaplasma Infections / Q000150:complications* / Q000378:metabolism / Q000382:microbiology; D016990:Ureaplasma urealyticum
chemical_list: D007166:Immunosuppressive Agents; D000641:Ammonia; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus