The bacteria and the host: a story of purinergic signaling in urinary tract infections.

The local environment forces a selection of bacteria that might invade the urinary tract, allowing only the most virulent to access the kidney. Quite similar to the diet in setting the stage for the gut microbiome, renal function determines the conditions for bacteria-host interaction in the urinary tract. In the kidney, the term local environment or microenvironment is completely justified because the environment literally changes within a few micrometers. The precise composition of the urine is a function of the epithelium lining the microdomain, and the microenvironment in the kidney shows more variation in the content of nutrients, ion composition, osmolality, and pH than any other site of bacteria-host interaction. This review will cover some of the aspects of bacterial-host interaction in this unique setting and how uropathogenic bacteria can alter the condition for bacteria-host interaction. There will be a particular focus on the recent findings regarding how bacteria specifically trigger host paracrine signaling, via release of extracellular ATP and activation of P2 purinergic receptors. These finding will be discussed from the perspective of severe urinary tract infections, including pyelonephritis and urosepsis.