Influence of acetohydroxamic acid on experimental Corynebacterium renale pyelonephritis

Abstract

The role of Corynebacterium renale urease in the establishment of pyelonephritis was studied by the oral administration of acetohydroxamic acid (AHA), a urease inhibitor, to experimentally infected rats. The bacteria were introduced by surgical insertion of a zinc disc containing 1 X 10(6) colony-forming units of C-renale into the urinary bladder whereas sterile discs were implanted in the bladders of the control animals. Daily administration of AHA via the drinking water did not halt the development of pyelonephritis. Larger doses, given by gavage, did accomplish this goal; that is, the pH of the urine was lowered, the number of colony-forming units of C. renale in the kidney was reduced drastically, and pyelonephritic lesions were observed in the kidney by light-microscopic examination. All experimental rats developed cystitis in varying degrees of severity. About 70% of the intact AHA given by gavage was excreted in the urine 24 h after administration of this compound. Rats implanted with a urease-negative mutant of C. renale displayed no signs of pyelonephritis but did develop cystitis.

Microbial ureases: significance, regulation, and molecular characterization.

“…However, the rats developed cystitis. This evidence suggests that the ammonia liberated from ureolysis causes the alkalinization of the urine and may account, in part, for the necrosis of kidney tissue associated with pyelonephritis (93,94).…”

“…Bovine pyelonephritis is caused by Corynebacterium renale (94), an organism that possesses an active urease. Infection with this microorganism resulted in alkaline urine, growth of Coryniebacteriiuin ren/ile from kidney homogenates and urine, and necrosis of the renal tissue (94).…”

“…Bovine pyelonephritis is caused by Corynebacterium renale (94), an organism that possesses an active urease. Infection with this microorganism resulted in alkaline urine, growth of Coryniebacteriiuin ren/ile from kidney homogenates and urine, and necrosis of the renal tissue (94). Subsequently, Jerusik et al (93) showed that in experimentally infected rats the use of acetohydroxamic acid at high doses reduced the urine pH, decreased the number of colony-forming units of Corynebacterium renale in the kidney, and halted necrosis of the kidney tissue.…”

Role of urease in the formation of infection stones: comparison of ureases from different sources

“…Inhibition of urease has been suggested as a means of preventing these clinical conditions (8,11,16). However, despite the fact that bacterial ureases are responsible, much of the experimental work has been done with ureases from vegetable sources (3,7,17), since there appears to be a tacit assumption that "urease" is a single entity.…”

Influence of iron on Corynebacterium renale-induced pyelonephritis in a rat experimental model

“…In an attempt to facilitate the study of the pathogenesis of C. renale-induced pyelonephritis, a rat experimental model was developed (9), and it was shown that the gross appearance and histological condition of the renal tissue of infected rats bore a close resemblance to that of the renal tissue of cows exhibiting signs of pyelonephritis. In addition, experimental infection in rats could be prevented (10) by the daily oral administration of the urease inhibitor acetohydroxamic acid, and evidence was presented to indicate that the powerful urease possessed by C. renale (12,15) could play a role in the pathogenesis of this disease.…”