A uropathogenic <i>E. coli</i> UTI89 model of prostatic inflammation and collagen accumulation for use in studying aberrant collagen production in the prostate
Hannah Ruetten, Jaskiran Sandhu, Brett Mueller, Peiqing Wang, Helen L. Zhang, Kyle A. Wegner, Mark Cadena, Simran Sandhu, Lisa L. Abler, Jonathan J. Zhu, Chelsea A. O’Driscoll, Britta Chelgren, Zunyi Wang, Tian Shen, Jonathan Barasch, Dale E. Bjorling, Chad M. Vezina
Abstract
Bacterial infection is one known etiology of prostatic inflammation. Prostatic inflammation is associated with prostatic collagen accumulation and both are linked to progressive lower urinary tract symptoms in men. We characterized a model of prostatic inflammation using transurethral instillations of Escherichia coli UTI89 in C57BL/6J male mice with the goal of determining the optimal instillation conditions, understanding the impact of instillation conditions on urinary physiology, and identifying ideal prostatic lobes and collagen 1a1 prostatic cell types for further analysis. The smallest instillation volume tested (50 µL) distributed exclusively to the bladder, 100- and 200-µL volumes distributed to the bladder and prostate, and a 500-µL volume distributed to the bladder, prostate, and ureter. A threshold optical density of 0.4 E. coli UTI89 in the instillation fluid was necessary for significant ( P < 0.05) prostate colonization. E. coli UTI89 infection resulted in a low frequency, high volume spontaneous voiding pattern. This phenotype was due to exposure to E. coli UTI89, not catheterization alone, and was minimally altered by a 50-µL increase in instillation volume and doubling of E. coli concentration. Prostate inflammation was isolated to the dorsal prostate and was accompanied by increased collagen density. This was partnered with increased density of protein tyrosine phosphatase receptor type C + , procollagen type I-α 1 + copositive cells and decreased density of α 2 -smooth muscle actin + , procollagen type I-α 1 + copositive cells. Overall, we determined that this model is effective in altering urinary phenotype and producing prostatic inflammation and collagen accumulation in mice.