Bacterial urinary tract infections: Urethral cholinergic chemosensory cells (UCCC)

• Applicant: Privatdozent Dr. Klaus Deckmann
• Subject Area: Reproductive Medicine, Urology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 544054869

Urinary tract infections (UTI) are among the most common bacterial infections worldwide. UTI include infections of the urethra (urethritis), bladder (cystitis), ureter (ureteritis), and kidneys (pyelonephritis). Recently, we have identified a new cell type in the urethra that we believe has an infection-protective role. Our preliminary work indicates that these urethral cholinergic chemosensory cells (UCCC) act as sentinels at the entrance of the urogenital tract, detecting the presence of potentially harmful substances (e.g., bitter substances or bacteria) via taste transduction cascade and initiating defense mechanisms via a cholinergic signaling pathway. The aim of this project is to clarify whether UCCC are really responsible for the initiation of defense mechanisms and whether the initiated defense mechanisms reduce the risk of UTI both in animal and in patients. For this purpose, we use specific stimulation of the UCCC utilizing DREADD technology and optogenics to investigate whether UCCC initiate neurogenic inflammation as a defense mechanism. In addition, with the help of a new mouse model for ascending UTI, it should be clarified whether UCCC change the relative risk of infection and thus play a protective role in ascending UTI. Moreover, a patient study will investigate whether gene polymorphisms in the taste receptor Tas2R38 or in TRPM5 (part of the taste cascade) have an impact on the risk of infection. Given the frequency of the disease, it is critically important to learn more about the fundamentals of the bacteria-host relationship and the mechanisms in the body that take place during UTI. This understanding could later form the basis for new therapeutic approaches.

• DFG Programme: Research Grants