# Ureaplasma urealyticum- and Ureaplasma parvum-associated hyperammonemia

> **NIH NIH R21** · MAYO CLINIC ROCHESTER · 2020 · $198,750

## Abstract

PROJECT SUMMARY
Hyperammonemia syndrome is a condition of previously unknown cause affecting approximately 4% of lung
transplant recipients early after transplantation. Despite maximal supportive therapy directed at suppressing
ammonia production and augmenting its excretion, most with this condition have historically progressed to
cerebral edema and died. Using PCR, we detected Ureaplasma urealyticum, a bacterium which produces large
amounts of urease, hypothetically leading to production of ammonia, in the blood and organs of a lung
transplant recipient who died of hyperammonemia syndrome. We subsequently tested lower respiratory
secretions, and/or lung tissue of 12 additional lung transplant recipients with hyperammonemia syndrome -
seven tested positive for U. urealyticum and the other five tested positive for Ureaplasma parvum. Although
seven diagnoses were made post-mortem, six were made while patients were alive, enabling treatment with
Ureaplasma-directed therapy; all six survived. Importantly, we have found no evidence of pulmonary or
systemic infection with these organisms in lung transplant recipients without hyperammonemia syndrome.
There is also evidence supporting donor-transmission of Ureaplasma species to lung transplant recipients.
Based on these clinical findings, we established immunosuppressed experimental murine models of U.
urealyticum and U. parvum infection, which we used to show that infected mice developed hyperammonemia.
We also performed antimicrobial susceptibility of Ureaplasma species, showing that it is not predictable (i.e.,
antibacterial resistance in Ureaplasma species is a challenge).
Together, our finding of U. urealyticum or U. parvum in all lung transplant recipients with hyperammonemia
syndrome tested to date, the ability of these organisms to generate ammonia from urea, and recapitulation of
hyperammonemia in animal models, suggest that U. urealyticum and U. parvum are likely causes of
hyperammonemia syndrome in lung transplant recipients. Notably, our preliminary studies suggest that
appropriately directed antimicrobial therapy can reverse this syndrome.
In our proposed studies, we will define mechanisms behind this unusual infection-associated metabolic
syndrome, including determining whether U. parvum and U. urealyticum can produce sufficient ammonia to
result in systemic hyperammonemia, and assessing how the immune system protects against Ureaplasma-
associated hyperammonemia. Using experimental animals, we will delineate antibiotic prevention and
treatment strategies for Ureaplasma-associated hyperammonemia, including cases associated with
antibacterial resistance. Our research team has a unique set of skills and experience to carry out the proposed
studies which will elucidate how a bacterium can cause a treatable metabolic syndrome in humans.

## Key facts

- **NIH application ID:** 9930732
- **Project number:** 1R21AI150649-01
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Robin Patel
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $198,750
- **Award type:** 1
- **Project period:** 2020-02-12 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930732

## Citation

> US National Institutes of Health, RePORTER application 9930732, Ureaplasma urealyticum- and Ureaplasma parvum-associated hyperammonemia (1R21AI150649-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9930732. Licensed CC0.

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