Role of Bacterial Urease in Experimental Pyelonephritis

Braude, Abraham I.; Siemienski, Jennie

doi:10.1128/jb.80.2.171-179.1960

Cited by 125 publications

(46 citation statements)

References 7 publications

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“…Second, as noted above, bacterial attachment may facilitate invasion of the renal parenchyma. The closely packed layers of adherent bacteria seen in this study may have injured the underlying epithelial cells, either through the cytotoxic effects of a bacterial product such as urease (23,28) or indirectly, by hydrolytic enzymes released from phagocytosing leukocytes (29). Adherence may also be a prerequisite for the intracellular penetration of intact mucosal cells.…”

Section: Phenomenon Also Occurs In Humans Amar Observed Calicotubulamentioning

confidence: 77%

“…Proteus also appeared capable of penetrating intact epithelial cells and it is possible that the organisms may have been passing through the cells in a manner similar to the mechanism whereby ShigeUa (8) or Salmonella (9) reach the intestinal submucosa. P. mirabilis may have a specific ability to parasitize renal epithelial cells as Braude and Siemienski have reported that monkey kidney epithelial cells grown in tissue culture are susceptable to intracellular colonization by P. mirabilis but not by E. coli (23). Finally, the discovery of bacteria in Bowman's space and in occasional tubular lumina suggest that bacteria may also reach the cortex as a result of calicotubular backflow.…”

Section: Discussionmentioning

confidence: 99%

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Host-Parasite Interaction in the Rat Renal Pelvis

Silverblatt

1974

The Journal of Experimental Medicine

138

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The major route by which bacteria are presumed to enter the kidney is in retrograde fashion from the bladder. This path is facilitated by means of vesicoureteral reflux, a phenomenon that takes place spontaneously in animals and man (1, 2). Hence the opportunity for establishing a nidus of infection must occur with relative frequency. Despite this seemingly penetrable physiologic barrier (i.e., reflux), the kidney is difficult to infect and procedures employing highly virulent organisms (3), trauma to the kidney (4), or obstruction to the urinary outflow (5) are necessary to produce intrarenal infection. This means that reflux per se is not synonymous with infection and bacterial colonization requires the penetration of an epithelial barrier by the organism. Based on this reasoning, whether or not infection takes place will depend upon the ability of the pelvic or tubular epithelium to resist invasion (6, 7).Little is known about the interaction between bacteria and the pelvic mucosal cells, however. On the epithelial surfaces, for example along the microvillous border of the intestine, adherence of ShigeUa (8), Salmonella (9), and Escherichia coli (10, 11) to the epithelial cell is an important first step for bacterial invasion, allowing organisms to concentrate in large numbers and to invade specific regions of the gut. In these infections transepithelial spread occurs by a process similar to phagocytosis; adherent organisms are enveloped by portions of the luminal plasma membrane and penetrate into the cytoplasm of the intestinal epithelial cells. One of the mechanisms by which these, as well as other gram-negative organisms adhere to epithelial surfaces is by means of filamentous appendages called pili (12)(13)(14). While possession of these structures is not necessarily correlated with virulence, such an association has been demonstrated for gonococci (15).To study the interaction between bacteria and the renal pelvic epithelium, the early phases of retrograde Proteus pyelonephritis were examined by light and

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Section: Phenomenon Also Occurs In Humans Amar Observed Calicotubulamentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Host-Parasite Interaction in the Rat Renal Pelvis

Silverblatt

1974

The Journal of Experimental Medicine

138

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“…Finally, interest in urease is due to the association of the enzyme with human disease. There are two sites of infection, the urinary tract {Braude and Siemienski, 1960;Griffith et al, 1976;Takeuchi et al, 1980) and the gastroduodenal region (Blaser, 1992), where bacterial ureases are thought to play a significant role in pathogenesis. At both sites, it is the production of ammonia that is important for the development of disease.…”

Section: Introductionmentioning

confidence: 99%

Bacterial ureases: structure, regulation of expression and role in pathogenesis

Collins

D’Orazio

1993

Molecular Microbiology

203

114

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The nickel metalloenzyme urease catalyses the hydrolysis of urea to ammonia and carbamate, and thus generates the preferred nitrogen source of many organisms. When produced by bacterial pathogens in either the urinary tract or the gastroduodenal region, urease acts as a virulence factor. At both sites of infection urease is known to enhance the survival of the infecting bacteria. Ammonia resulting from the action of urease is believed to increase the pH of the environment to one more favourable for growth, and to injure the surrounding epithelial cells. In addition, in the urinary tract urease activity can result in the formation of urinary calculi. Bacterial urease gene clusters contain from seven to nine genes depending upon the species. These genes encode the urease structural subunits and accessory polypeptides involved in the biosynthesis of the nickel metallocentre. So far, three distinct mechanisms of urease gene expression have been described for ureolytic bacteria. Some species constitutively produce urease; some species produce urease only if urea is present in the growth medium; and some species produce urease only during nitrogen-limiting growth conditions. For either the urea-inducible genes or the nitrogen-regulated genes transcription appears to be positively regulated. In the nitrogen-regulated systems, urease gene expression requires Nac (nitrogen assimilation control), a member of the LysR family of transcriptional activators. Urea dependent expression of urease requires UreR (urease regulator), a member of the AraC family of transcriptional activators. An evolutionary tree for urease genes of eight bacterial species is proposed.

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“…If the organism is a strain of Proteus producing the enzyme urease, urea in the urine is broken down to ammonia and the pH of the urine is increased, thus favouring the precipitation of relatively insoluble crystalloids which with the foreign body as a nucleus eventually form massive urinary calculi. (The role of bacterial urease in pyelonephritis has been studied experimentally by Braude & Siemienski, 1960. ) Presumably pressure of urine due to the obstruction in the bladder spreads the infection to the kidneys via the ureters, leading to renal failure and death.…”

Section: Discussionmentioning

confidence: 99%

Proteus Vulgaris Urinary Tract Infections in Rats; Treatment With Nitrofuran Derivatives

Hossack

1962

British Journal of Pharmacology and Chemotherapy

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Ascending urinary tract infections with stone formation have been produced experimentally in rats, using a modification of the method of Vermuelen & Goetz (1954a, b). A zinc disc infected with a culture of Proteus vulgaris was inserted into the bladder by suprapubic cystotomy under ether anaesthesia. The pH of the urine rises from 6.9 to 8 or 9 and calculi develop in the bladder within a few days of infection. The bladder and ureters become swollen, distended and inflamed, and renal abscesses develop. Death from renal failure generally occurs within 10 days of infection. Oral treatment with nitrofurantoin was commenced three days after infection and continued for one month. This arrested the initial rise in urine alkalinity and stone formation, and few, if any, macroscopic lesions were found at post‐mortem examination. Of nine nitrofuran derivatives examined for activity against this infection several showed slight activity, but only one, N‐(5‐Nitrofurfurylidene)‐γ‐butyric acid, was as active as nitrofurantoin when given at four times the dose, but it was also one‐third as toxic. It is concluded that this technique is suitable for the examination of potential urinary antiseptics.

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Role of Bacterial Urease in Experimental Pyelonephritis

Cited by 125 publications

References 7 publications

Host-Parasite Interaction in the Rat Renal Pelvis

Host-Parasite Interaction in the Rat Renal Pelvis

Bacterial ureases: structure, regulation of expression and role in pathogenesis

Proteus Vulgaris Urinary Tract Infections in Rats; Treatment With Nitrofuran Derivatives

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