Ureaplasma-driven morbidity in preterm infants: Can we identify underlying mechanisms of Ureaplasma-mediated inflammation?

• Applicant: Privatdozentin Dr. Kirsten Glaser
• Subject Area: Pediatric and Adolescent Medicine ; Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 556976345

Substantial evidence exists that perinatal and postnatal Ureaplasma exposure of preterm infants is associated with an increased isk for adverse inflammation and the development of inflammation-mediated short-term and long-term morbidity, especially the development of bronchopulmonary dysplasia. Experimental data have long been scarce – in large part due to difficulties in culture growth of Ureaplasma species. The applicant has successfully established different in vitro models of Ureaplasma infection using viable Ureaplasma isolates that confirmed considerable pro-inflammatory and pro-apoptotic capacity of Ureaplasma as well as a disturbance of cytokine equilibrium upon Ureaplasma infection in vivo and in vitro. The current project aims at characterizing underlying mechanisms of Ureaplasma-driven early immune response in neonatal monocytes representing key mediators of early neonatal inflammation. To the best of our knowledge, this is the first study to analyze the interaction of Ureaplasma isolates with toll-like receptors (TLR) and TLR-related signaling molecules in neonatal monocytes. Patterns of TLR expression and phosphorylation of key signaling molecules will be assessed by means of qRT-PCR, multi-color flow cytometry, western blotting, and multi-analyte immunoassay. Comparative analyses in preterm, term and adult monocytes will test for gestational age-dependent differences of Ureaplasma-mediated immune response. Given the potential role of Ureaplasma membrane lipoproteins as virulence factors associated with host immune response, stimulation assays will evaluate the pro-inflammatory capacity of a recombinant Ureaplasma lipoprotein, and Ureaplasma membrane lipoproteins fractions extracted at the applicant’s lab. Finally, stimulation assays with common ATCC isolates compared to Ureaplasma serovars isolated from clinical specimens of preterm infants with systemic Ureaplasma infection will examine potential serovar-specific differences of Ureaplasma virulence. These serovars were isolated in a prospective study conducted by the applicant. Ultimately, investigations will address the question of whether exposure of preterm and term neonatal monocytes to higher exogenous urea concentrations impacts the pro-inflammatory capacity of Ureaplasma species – corresponding to the potential promotion of disease manifestation by variable amniotic fluid and airway urea concentrations in individual patients. This project is supposed to contribute to a better knowledge of Ureaplasma-induced neonatal inflammation and may allow the identification of addressable risk factors and signaling pathways and might push forward the implementation of screening practices and the development of targeted anti-inflammatory and/or anti-infective strategies.

• DFG Programme: Research Grants