Urease, Urolithiasis, and Colonization of the Urinary Tract

Abstract

In urinary tracts with functional or anatomical abnormalities in which the normal flow of urine is disrupted or in which residual urine cannot be expressed from the bladder, a distinct group of bacterial species may cause infection. These infections are most frequently polymicrobial. The placement of a long-term indwelling catheter ensures that a urinary tract infection (UTI) will develop. Proteus mirabilis, a dimorphic gram-negative bacterium, commonly causes UTI in individuals with structural abnormalities or long term catheterization, i.e., complicated UTI. Flagella and the mannose-resistant, Proteus-like (MR/P) fimbriae and P. mirabilis fimbriae (PMF) have been identified as virulence factors of P. mirabilis that contribute to its colonization of the urinary tract in a murine model. Urease inhibitors have been used to treat patients with urolithiasis. The level of bladder colonization by the urease-negative mutant was >200-fold higher in the catheterized mice than in the uncatheterized mice. Despite the successful colonization of the bladders of the catheterized mice by the urease-negative mutant, urolithiasis or death was never observed. The low-level urease activity detected in the uninduced culture of the wild type is consistent with a previous finding that the expression of UreD is not as tightly regulated in P. mirabilis as it is in Escherichia coli expressing cloned urease genes.