Potential Role of Extracellular ATP Released by Bacteria in Bladder Infection and Contractility

Area of Science:

• Microbiology
• Urology
• Cell Biology

Background:

• Urgency urinary incontinence (UUI) and overactive bladder (OAB) are conditions potentially influenced by the urinary tract's bacterial inhabitants.
• The micturition process involves complex neural signaling and detrusor muscle contraction in response to bladder filling.

Purpose of the Study:

• To model host responses to urogenital bacteria and investigate their impact on bladder function.
• To explore the role of bacterial metabolites, particularly ATP, in modulating urothelial and myofibroblast activity.

Main Methods:

• Utilized urothelial bladder cell lines and myofibroblast contraction assays.
• Measured calcium (Ca²⁺) influx, gene expression, and alpha smooth muscle actin deposition.
• Analyzed extracellular ATP levels and the effects of bacterial supernatants.

Main Results:

• Uropathogens like *Escherichia coli* and *Gardnerella vaginalis* significantly induced Ca²⁺ influx and cell contraction.
• *Lactobacillus crispatus* and *L. gasseri* did not induce these responses and their supernatants inhibited pathogen-induced effects.
• Bacterial induction of Ca²⁺ influx and contraction correlated with extracellular ATP production by *E. coli*.

Conclusions:

• Commensal bacteria, such as lactobacilli, may mitigate UUI and OAB symptoms by interfering with pathogen-induced signaling pathways, potentially through ATP utilization or inhibitory compound production.
• Bacterial ATP release can act as a virulence factor, impacting urothelial signaling and potentially contributing to UUI and OAB.
• Targeted strategies to enhance beneficial commensal bacteria and reduce pathogen-derived ATP may offer new therapeutic avenues for UUI and OAB.