The significance of urease in proteus pyelonephritis: A bacteriological study

Maclaren, D. M.

doi:10.1002/path.1700960106

Cited by 58 publications

(30 citation statements)

References 16 publications

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“…The mechanism of pathogenesis is unclear, but several virulence properties have been cited (31) and include motility (28), a uroepithelial cell adhesin (45), fimbriae (1. 9, 27, 37-39), hemolysin production (15,29,44), ability to invade kidney epithelium (4,19,30), and production of urease (4,10,13,18,19).Animal models of pyelonephritis have been used to implicate urease as a contributing factor to the severity of infection. Braude and Siemienenski (4), using a rat model of pyelonephritis, demonstrated that urease-positive representatives of the Proteeae tribe colonized kidney epithelium more avidly than did Escherichia (oli and Pseudomonas aeruginosa and produced more severe histological damage than enterococci.…”

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“…Braude and Siemienenski (4), using a rat model of pyelonephritis, demonstrated that urease-positive representatives of the Proteeae tribe colonized kidney epithelium more avidly than did Escherichia (oli and Pseudomonas aeruginosa and produced more severe histological damage than enterococci. MacLaren (18) used an ethylmethane sulfonate-generated urease mutant of P. mirabilis in a mouse model of pyelonephritis and found that renal failure and death were caused by the parent strain but only rarely by the urease-negative mutant.…”

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Proteus mirabilis urease: genetic organization, regulation, and expression of structural genes

1988

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Proteus mirabilis, a cause of serious urinary tract infection, produces urease, an important virulence factor for this species. The enzyme hydrolyzes urea to CO2 and NH3, which initiates struvite or apatite stone formation. Genes encoding urease were localized on a P. mirabilis chromosomal DNA gene bank clone in Escherichia coli by deletion analysis, subcloning, Bal31 nuclease digestion, transposon TnS mutagenesis, and in vitro transcription-translation. A region of DNA between 4.0 and 5.4 kilobases (kb) in length was necessary for urease activity and was located within an 18.5-kb EcoRI fragment. The operon was induced by urea and encoded a multimeric, cytoplasmic enzyme comprising subunit polypeptides of 8,000, 10,000, and 73,000 daltons that were encoded by a single polycistronic mRNA and transcribed in that order. Seventeen urease-negative transposon insertions were isolated that synthesized either none of the structural subunit polypeptides, the 8,000-dalton polypeptide alone, or both the 8,000-and 10,000-dalton subunit polypeptides. The molecular weight of the native enzyme was estimated to be 212,000 by Superose-6 chromatography. Homologous sequences encoding the urease of Providencia stuartii synthesized subunit polypeptides of similar sizes and showed a similar genetic arrangement. However, restriction maps of the operons from the two species were distinct, indicating significant divergence.Proteus mirabilis, a common cause of urinary tract infection in both catheterized and noncatheterized patients (9,24,34,43), can result in serious complications, including cystitis, prostatitis, urolithiasis, pyelonephritis, and bacteremia (34, 42). The mechanism of pathogenesis is unclear, but several virulence properties have been cited (31) and include motility (28), a uroepithelial cell adhesin (45), fimbriae (1. 9, 27, 37-39), hemolysin production (15,29,44), ability to invade kidney epithelium (4,19,30), and production of urease (4,10,13,18,19).Animal models of pyelonephritis have been used to implicate urease as a contributing factor to the severity of infection. Braude and Siemienenski (4), using a rat model of pyelonephritis, demonstrated that urease-positive representatives of the Proteeae tribe colonized kidney epithelium more avidly than did Escherichia (oli and Pseudomonas aeruginosa and produced more severe histological damage than enterococci. MacLaren (18) used an ethylmethane sulfonate-generated urease mutant of P. mirabilis in a mouse model of pyelonephritis and found that renal failure and death were caused by the parent strain but only rarely by the urease-negative mutant.In addition, bacterial urease is recognized as a virulence factor because of its role in kidney and bladder stone formation (10). Alkalinization of the urine by hydrolysis of urea to ammonia and carbon dioxide facilitates precipitation of polyvalent cations and anions, primarily struvite, MgNH4PO4 .6H20 and carbonate-apatite, Ca1(PO04CO3 OH)6(OH). The proportion of stones formed due to infection has been estimated at between 20 an...

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Proteus mirabilis urease: genetic organization, regulation, and expression of structural genes

1988

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“…Another is urea, a growth stim-VOL. 75, 2007 MINIREVIEWS 4195 ulant for Proteus mirabilis that causes severe kidney infections (3,38). It is also recognized that lack of certain nutrients can induce bacterial mechanisms for acquiring them, e.g., production of siderophores and cell wall receptors for iron-bearing transferrins by gram-negative bacteria when they lack available iron (74).…”

Section: New Concepts Of the Role Of Metabolites In Pathogenicity Arimentioning

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Effect of Host Lactate on Gonococci and Meningococci: New Concepts on the Role of Metabolites in Pathogenicity

2007

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2In 1988, Britigan and colleagues (4) showed that the lactate in human neutrophils stimulated oxygen consumption by Neisseria gonorrhoeae and suggested that this might impair their oxygen-dependent bactericidal mechanisms. This first indication that lactate metabolism might be important in the pathogenicity of N. gonorrhoeae has been amply confirmed during the past decade (17,61,77), and now lactate has been shown to have important effects on Neisseria meningitidis (15,16). This review uses the work on gonococci as background to describe recent research on the meningococcus, which in turn provided the key to proving the influence of lactate on gonococcal pathogenicity in vivo. Studies on N. meningitidis showed that, in addition to a general stimulation of metabolism, lactate promotes the production of specific determinants of pathogenicity. Some differences between meningococci and gonococci in their responses to lactate are discussed, and new concepts of the role of metabolites in pathogenicity arising from the work are summarized. Throughout this review, it should be kept in mind that lactate is present in urogenital and respiratory secretions, blood, phagocytes, and cerebrospinal fluid (CSF), together with glucose and pyruvate (61), two other energy sources used effectively by gonococci and meningococci (37,42,43). Hence, in vivo, gonococci and meningococci grow on a mixture of carbon sources. To mimic this situation, most of the studies described deal with the influence of lactate on gonococci and meningococci growing in media containing glucose. STIMULATION OF GONOCOCCAL METABOLISM BY LACTATE: THE MECHANISM INVOLVED AND RELATION TO PATHOGENICITYThe original observations of the potential importance of lactate on the behavior of N. gonorrhoeae were reinforced by the demonstration that lactate in blood cell extracts enhanced the sialylation of gonococcal lipopolysaccharide (LPS) by cytidine-5Ј-monophospho-N-acetyl neuraminic acid (CMP-NANA) (49). Previous observations of gonococci harvested from urethral exudates had shown that host-derived CMP-NANA was incorporated into their LPS, rendering them resistant to killing by complement-mediated lysis in human serum, by phagocytes, and by antibody (24, 60). The enhancing effect of physiological concentrations of lactate on LPS sialylation occurred as gonococci were emerging from lag phase in a medium containing glucose. This resulted from an overall stimulation of metabolism, evidenced by greater LPS production (by 10 to 20%), enhanced protein synthesis (10 to 20%), and larger pentose contents (30 to 60%) (21, 22). Increased LPS sialylation occurs through greater production of both LPS and the sialyltransferase. There was more rapid emergence from lag phase with lactate and a 20% increase in the rate of logarithmic growth compared with glucose alone (22). Lactate was used more rapidly than glucose in a synthetic medium (22), as was seen in the fluid obtained from subcutaneous plastic chambers in guinea pigs that had been infected with gonococci (25).The mechanisms o...

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“…The severity and persistence of Proteus infections are attributed to the presence of urease while urease-negative E. coli infections are generally milder and transistory [1,2,4,7]. The infectivity of urease-negative Proteus mutants was shown, however, to be comparable to that of the parent strains in causing experimental pyelonephritis [5]; nonetheless, once infection by the urease negative mutants had become established, the course of the infection was milder than with urease …”

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Prevention of Ascending Pyelonephritis in Mice by Urease Inhibitors

Aronson

Medalia

Griffel³

1974

Nephron

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The effect of 2 urease inhibitors, hydroxyurea and thiourea, on experimental ascending pyelonephritis by P. mirabilis was studied in mice undergoing water diuresis. It was found that hydroxyurea significantly diminished the number of bacteria in the kidneys, the severity and number of lesions as well as the number of excreted bacteria. Thiourea, a weaker inhibitor, was less effective. The drugs prevented the establishment of infections but did not eliminate already existing ones. The mechanisms of hydroxyurea action were studied, as this drug also inhibits DNA synthesis. Hydroxyurea did not prevent infections by (urease-negative) E. coli, and selectively suppressed P. mirabilis in a mixed infection with E. coli.

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The significance of urease in proteus pyelonephritis: A bacteriological study

Cited by 58 publications

References 16 publications

Proteus mirabilis urease: genetic organization, regulation, and expression of structural genes

Proteus mirabilis urease: genetic organization, regulation, and expression of structural genes

Effect of Host Lactate on Gonococci and Meningococci: New Concepts on the Role of Metabolites in Pathogenicity

Prevention of Ascending Pyelonephritis in Mice by Urease Inhibitors

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