Contribution of Uremia to Ureaplasma-Induced Hyperammonemia

Lung transplant recipients (LTRs) are vulnerable to unexplained hyperammonemia syndrome (HS) in the early post-operative period, a condition typically unresponsive to non-antibiotic interventions. Recently, we showed that HS in LTRs is strongly correlated with Ureaplasma infection of the respiratory tract. It is not well-understood what makes LTRs preferentially susceptible to this phenomenon, compared to other immunocompromised hosts. Ureaplasma species harbor highly active ureases that convert urea to ammonia and CO2, utilizing the generated transmembrane potential to synthesize ATP. Post-operative LTRs commonly experience renal failure, resulting in uremia. We hypothesized that uremia could be a potentiating comorbidity to the development of HS secondary to Ureaplasma infection in LTRs by providing increased substrate for ureaplasmal ureases. We designed a novel dialyzed flow system to test the ammonia producing capacity of four isolates of Ureaplasma parvum and six isolates of Ureaplasma urealyticum in media formulations relating to normal and uremic host conditions. For all isolates, growth under uremic conditions resulted in significantly increased ammonia production over 24 hours, despite similar end-point bacterial quantities. Specifically, the isolates produced, on average, 1776.52 [standard deviation=263.98] mol/L more ammonia when grown under uremic compared to normal conditions. This suggests that uremia, common in early post-operative LTRs, is a plausible contributing factor to the phenomenon of Ureaplasma-induced HS in this patient population.