Potential role of extracellular ATP released by bacteria in bladder infection and contractility

Abstract

Urgency urinary incontinence (UUI), the result of conditions such as overactive bladder (OAB), could potentially be influenced by both commensal and urinary tract infection-associated bacteria. The sensing of bladder filling involves interplay between various parts of the nervous system eventually resulting in contraction of the detrusor muscle during micturition. Here we model host responses to various urogenital bacteria, firstly by using urothelial bladder cell lines and then with myofibroblast contraction assays. To measure responses, we examined calcium influx, gene expression and alpha smooth muscle actin deposition assays. We found that organisms such as Escherichia coli and Gardnerella vaginalis strongly induced calcium influx and contraction, whereas, Lactobacillus crispatus and L. gasseri did not induce this response. Additionally, supernatants from lactobacilli impeded influx-and contraction induced by the uropathogens. Upon further investigation of factors associated with the purinergic signaling pathways, we found that influx and contraction of cells correlated to the amount of extracellular ATP produced by E. coli. Certain lactobacilli appear to mitigate this response by utilizing extracellular ATP or producing inhibitory compounds which can act as a receptor agonist or calcium channel blocker. These findings suggest that members of the urinary microbiota may be influencing UUI.