Role of Urease in Pyelonephritis Resulting from Urinary Tract Infection with Proteus

Abstract

The role of urease in induction of pyelonephritis was studied by treatment of proteus-infected rats with acetohydroxamic acid, a potent inhibitor of urease. Infection was produced by introduction of Proteus mirabilis into the bladder along with a zinc disk. Controls were treated identically but received no acetohydroxamic acid. The number of bacteria per milliliter of urine was the same in both groups. The number of bacteria in the kidneys and the extent of renal damage was much greater in controls. Common enterobacteraceal antigen was not detected in the renal parenchyma of rats treated with acetohydroxamic acid. Treatment with acetohydroxamic acid thus prevented invasion of and damage to kidney tissue without reduction of urinary infection. Thus new evidence was found that the invasive properties of Proteus in the urinary tract are dependent on alkalinization of urine by urease and the resulting damage to the renal epithelium.

The high-affinity phosphate transporter Pst in Proteus mirabilis HI4320 and its importance in biofilm formation

“…Clinical syndromes associated with P. mirabilis include cystitis and pyelonephritis, with possible complications from stone formation and bacteraemia (Mobley, 1996). These micro-organisms survive in the urinary tract by virtue of their production of a battery of virulence factors, including urease, flagella, fimbriae, haemolysin and IgA protease (Belas, 1996;Mobley et al, 1994;Musher et al, 1975;Peerbooms et al, 1984; Walker et al., 1999), and formation of crystalline biofilm on indwelling catheters (Stickler et al, 1993).…”

“…Clinical syndromes associated with P. mirabilis include cystitis and pyelonephritis, with possible complications from stone formation and bacteraemia (Mobley, 1996). These micro-organisms survive in the urinary tract by virtue of their production of a battery of virulence factors, including urease, flagella, fimbriae, haemolysin and IgA protease (Belas, 1996;Mobley et al, 1994;Musher et al, 1975;Peerbooms et al, 1984; Walker et al., 1999), and formation of crystalline biofilm on indwelling catheters (Stickler et al, 1993).Biofilm formation -one of the most important mechanisms of pathogenicity of this micro-organism in the urinary tract -may be defined as a community of surface-attached bacteria encased in an extracellular matrix consisting of secreted carbohydrates, proteins and DNA. Indeed, biofilms have been associated with the virulence of a number of pathogens (Castelli et al, 2006).…”

The urease enzymes of Campylobacter pylori and a related bacterium

“…Urease enzymes have since been isolated and purified from many species of bacteria, in which they play an important role in nitrogen metabolism. The ability to hydrolyse urea has several consequences for mammalian hosts colonised by urease-positive micro-organisms, including : regulation of transfer of endogenous urea across the rumen wall ; an effect upon the nitrogen metabolism of ruminants (Wozny et al, 1977); production of urinary stones (Griffith and Musher, 1973); and contribution to the pathogenesis of pyelonephritis (Braude and Siemienski, 1960;Musher et al, 1975).…”

Proteus morgani is less frequently associated with urinary tract infections than Proteus mirabilis--an explanation

“…are common and some strains have a special predilection for the upper urinary tract (Fairley et al, 1971). Urease is thought to be a major virulence factor because it degrades urea, releasing ammonia, which may cause damage and death to the renal epithelium, inactivation of complement, and conditions favouring the development of renal stones (Braude and Siemienski, 1960;Musher et al, 1975). Urease is produced in large amounts by P. morguni and P .…”