About 50% of women and 14% of men will have a urinary tract infection (UTI) in their lifetime, and approximately a quarter of women with a UTI will develop recurrent UTI (rUTI).  Evidence from rodent models supports that rUTIs may be due to intracellular bacterial communities (IBCs), large and dense intracellular aggregates of 104 to 106  bacteria, in bladder uroepithelium by uropathogenic Escherichia coli (UPEC) and other bacteria.  Despite the strong evidence for IBCs in the pathophysiology of rUTI and chronic cystitis in rodent models, IBCs have never been demonstrated in the human urinary bladder.  We sought to assess for the presence of intracellular bacterial communities (IBCs) in the human urinary bladder.  We hypothesized that IBCs will be demonstrable in our patient cohort undergoing cystectomy.

Patients who were undergoing simple cystectomy for non-oncological indications were consented via IRB-approved protocol.  Patient demographics were collected prospectively.  Following bladder removal, a portion of bladder tissue was saved for laboratory analysis using scanning and transmission electron microscopy.  In addition, a urine specimen was collected from each patient prior to surgery.

Twelve patients were enrolled in this prospective study.  Each had matching bladder tissue and urine specimens available for analysis.  One urine and bladder specimen had been analyzed with electron microscopy at the time of this writing.  The specimens analyzed were from the bladder dome of a 58 year old male with high-risk neurogenic lower urinary tract dysfunction and recurrent refractory urinary tract infections, for which he was on cefepime and flagyl until the time of surgery.  Intraoperative findings including a thickened bladder wall and contracted bladder.  Scanning electron microscopy of the urine specimen demonstrated the diffuse presence of bacteria.  Scanning electron microscopy demonstrated uroepithelial cells with the appearance of blebs harboring IBCs (Figure left), similar to those seen in rodent models.  Transmission electron microscopy, employed with the goal of visualizing an  IBC in section, did not clearly demonstrate intracellular bacteria, but showed multiple collagen fibers (Figure right) consistent with an end stage bladder with neurogenic lower urinary tract dysfunction.  Subsequent electron microscopy and immunohistochemistry analysis will further evaluate bladder and urine specimens for the presence or absence of IBCs.

A human urinary bladder specimen had appearance consistent with the presence of IBCs.  Additional analysis of the present cohort, and corroborative immunohistochemical investigations are ongoing.

The identification of the presence or absence of IBCs in human bladder tissue will have major implications for preventative therapy and treatment of recurrent UTI, and may set the groundwork for targeting IBCs with adjunctive therapeutic or preventative strategies.