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bioRxiv · 10.1101/2020.08.10.238196

A Uropathogenic E. coli UTI89 model of prostatic inflammation and collagen accumulation for use in studying aberrant collagen production in the prostate

RUETTEN, H. M.·Sandhu, J.·Mueller, B.·Wang, P.·Zhang, H. L.·Wegner, K. A.·Cadena, M.·Sandhu, S.·Abler, L.·Zhu, J.·O'Driscoll, C. A.·Chelgren, B.·Wang, Z.·Shen, T.·Barasch, J.·Bjorling, D. E.·Vezina, C. M.
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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 utilizing transurethral instillations of E. 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 {micro}L) distributes exclusively to bladder, 100 and 200 {micro}L volumes distributes to bladder and prostate, and a 500 {micro}L volume distributes to bladder, prostate and ureter. A threshold optical density (OD) of 0.4 E. coli UTI89 in the instillation fluid is necessary for significant (p < 0.05) prostate colonization. E. coli UTI89 infection results in a low frequency, high volume spontaneous voiding pattern. This phenotype is due to exposure to E. coli UTI89, not catheterization alone, and is minimally altered by a 50 {micro}L increase in instillation volume and doubling of E. coli concentration. Prostate inflammation is isolated to the dorsal prostate and is accompanied by increased collagen density. This is partnered with increased density of PTPRC+, ProCOL1A1+ co-positive cells and decreased density of ACTA2+, ProCOL1A1+ co-positive cells. Overall, we determined that this model is effective in altering urinary phenotype and producing prostatic inflammation and collagen accumulation in mice.

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RUETTEN, H. M., Sandhu, J., Mueller, B., Wang, P., Zhang, H. L., Wegner, K. A., Cadena, M., Sandhu, S., Abler, L., Zhu, J., O'Driscoll, C. A., Chelgren, B., Wang, Z., Shen, T., Barasch, J., Bjorling, D. E., Vezina, C. M.. 2020-08-10. A Uropathogenic E. coli UTI89 model of prostatic inflammation and collagen accumulation for use in studying aberrant collagen production in the prostate. https://doi.org/10.1101/2020.08.10.238196

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