Chapter 29 : The Tao of Urease

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This chapter describes the role of bacterial urease in infection, the structure of urease, and the genetic organization and regulation of urease genes. When urease is produced by uropathogens in an infected urinary tract, the hydrolysis of urea increases the ammonia concentration in the urine, and there is a subsequent elevation of the urine pH. The exact mechanism responsible for the increased level of survival of the pathogen and the damage associated with urease can only be inferred. Increased bacterial colonization of the urinary tract might result from the generation of an easily assimilated nitrogen source and/or from alkalinization of the urine to a more favorable pH for growth. Urease is produced in abundance by , a gram-negative curved or spiral bacterium that lives in the mucous layer overlaying the gastric epithelium. -infected gastric mucosa is characterized by a predominant neutrophil accumulation, and ammonia is thought to enhance a neutrophil-dependent cytocidal activity. The species urease gene cluster appears to code for more accessory polypeptides than are found in and species urease gene clusters. Expression of the plasmid-encoded urease genes appears to be regulated by a transcriptional activator termed UreR. Analysis of the chromosomal locus indicates that it contains only seven of the urease genes, , , , , , , and . Therefore, in contrast to the inducible gene clusters, no additional gene products are required for the constitutive expression of urease in .

Citation: Collins C. 1994. The Tao of Urease, p 437-449. In Miller V, Kaper J, Portnoy D, Isberg R (ed), Molecular Genetics of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818340.ch29

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Urinary Tract Infections
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Figure 1

Role of urease in the formation of struvite stones. Adapted from Griffith and Osborne ( ). Reprinted with permission of S. Karger AG, Basel.

Citation: Collins C. 1994. The Tao of Urease, p 437-449. In Miller V, Kaper J, Portnoy D, Isberg R (ed), Molecular Genetics of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818340.ch29
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Figure 2

Maps of various bacterial urease gene clusters. Shown are the relative sizes and orientations of the chromosomal urease genes ( ), and urease genes ( ), the plasmid-encoded and urease genes ( ), urease genes ( ), and sp. strain TB-90 urease genes ( ). Open boxes indicate the positions of each gene (). The oval represents Nac, the nitrogen assimilation control protein ( ). The arrow points to the Nac-binding site, located approximately 90 nucleotides upstream of in ( ).

Citation: Collins C. 1994. The Tao of Urease, p 437-449. In Miller V, Kaper J, Portnoy D, Isberg R (ed), Molecular Genetics of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818340.ch29
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Figure 3

Similarity between the amino acid sequences of UreA (structural subunit) and UreD (accessory polypeptide) from various bacterial species. A dendrogram representation of the clustering relationships between the amino acid sequences is shown. The horizontal branch lengths are proportional to the similarities between the sequences. A pairwise alignment of the sequences was performed by the algorithm of Needleman and Wunsch ( ) by using a re-scaled version of the scoring matrix of Dayhoff et al. ( ), as found in the Genetics Computer Group Sequence Analysis Software package, version 7.0.2 ( ). The similarity scores obtained were used to create a clustering order by the unweighted pair-group method by using arithmetic averages ( ). For the first 101 amino acids of UreA were analyzed UreH is thought to be equivalent to UreD of the other clusters.

Citation: Collins C. 1994. The Tao of Urease, p 437-449. In Miller V, Kaper J, Portnoy D, Isberg R (ed), Molecular Genetics of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818340.ch29
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1. Beeson, P. B.,, and D. Rowley. 1959. The anticomplementary effect of kidney tissue. Its association with ammonia production. J. Exp. Med. 110:695698.
2. Bender, R. A. 1991. The role of the NAC protein in the nitrogen regulation of Klebsiella aerogenes. Mol. Microbiol. 5:25752580.
3. Bender, R. A.,, P. M. Snyder,, R. Bueno,, M. Quinto,, and B. Magasanik. 1983. Nitrogen regulation system of Klebsiella aerogenes: the nac gene. J. Bacteriol. 156:444446.
4. Blaser, M. J. 1992. Helicobacter pylori: its role in disease. Clin. Infect. Dis. 15:386393.
5. Braude, A. I.,, and J. Siemienski. 1960. Role of bacterial urease in experimental pyelonephritis. J. Bacteriol. 80:171179.
6. Breitenbach, J. M.,, and R. P. Hausinger. 1988. Proteus mirabilis urease: partial purification and inhibition by boric acid and boronic acids. Biochem. J. 250:917920.
7. Collins, C. M. Unpublished data.
8. Collins, C. M.,, and S. Falkow. 1990. Genetic analysis of Escherichia coli urease genes: evidence for two distinct loci. J. Bacteriol. 172:71387144.
9. Collins, C. M.,, and D. Gutman. Unpublished data.
10. Collins, C. M.,, and D. M. Gutman. 1992. Insertional inactivation of an Escherichia coli urease gene by 1S3411. J. Bacteriol. 174:883888.
11. Collins, C. M.,, D. M. Gutman,, and H. Laman. 1993. Identification of a nitrogen-regulated promoter controlling expression of Klebsiella pneumoniae urease genes. Mol. Microbiol. 8:187198.
12. Cussac, V.,, R. L. Ferrero,, and A. Labigne. 1992. Expression of Helicobacter pylori urease genes in Escherichia coli grown under nitrogen-limiting conditions. J. Bacteriol. 174:24662473.
13. Dayhoff,' M. O.,, R. M. Schwartz,, and B. C. Orcutt,. 1978. Matrices for detecting distant relationships, p. 353358. In M. O. Dayhoff (ed.), The Atlas of Protein Sequence and Structure. National Biomedical Research Foundation, Washington, D.C..
14. Delisle, G. J. 1977. Multiple forms of urease in cytoplasmic fractions of Ureaplasma urealyticum. J. Bacteriol. 130:13901392.
15. Devereux, J.,, P. Haeberli,, and O. Smithies. 1984. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 12:387395.
16. DeVivo, M. J.,, P. R. Fine,, G. R. Cutter,, and H. M. Maetz. 1984. The risk of renal calculi in spinal cord injury patients. J. Urol. 131:857860.
17. Dixon, N. E.,, R. L. Blakeley,, and B. Zerner. 1980. Jack bean urease (EC III. The involvement of active-site nickel ion in inhibition by β-mercaptoethanol, phosphoramidate, and fluoride. Can. J. Biochem. 58:481488.
18. D'Orazio, S. E. F.,, and C. M. Collins. Unpublished data.
19. D'Orazio, S. E. F.,, and C. M. Collins. 1993. Characterization of a plasmid-encoded urease gene cluster found among members of the family Enterobacteriaceae. J. Bacteriol. 175:18601864.
20. D'Orazio, S. E. F.,, and C. M. Collins. 1993. The plasmid-encoded urease gene cluster of the Enterobacteriaceae is positively regulated by UreR, a member of the AraC family of transcriptional activators. J. Bacteriol. 175:34593467.
21. Dunn, B. E.,, G. P. Campbell,, G. I. Perez-Perez,, and M. J. Blaser. 1990. Purification and characterization of urease from Helicobacter pylori. J. Biol. Chem. 265:94649469.
22. Eaton, K.,, C. L. Brooks,, D. R. Morgan,, and S. Krakowka. 1991. Essential role of urease in pathogenesis of gastritis induced by Helicobacter pylori in gnotobiotic piglets. Infect. Immun. 59: 24702475.
23. Fowler, J. E. J. 1984. Bacteriology of branched renal calculi and accompanying urinary tract infection. J. Urol. 131:213215.
24. Friedrich, B.,, and B. Magasanik. 1977. Urease of Klebsiella aerogenes: control of its synthesis by glutamine synthetase. J. Bacteriol. 131:446452.
25. Gallegos, M.-T.,, C. Michan,, and J. L. Ramos. 1993. The XylS/AraC family of regulators. Nucleic Acids Res. 21:807810.
26. Gatermann, S.,, J. John,, and R. Marre. 1988. Staphylococcus saprophyticus urease: characterization and contribution to uropathogenicity in unobstructed urinary tract infection of rats. Infect. Immun. 57:110116.
27. Gatermann, S.,, and R. Marre. 1989. Cloning and expression of Staphylococcus saprophyticus urease gene sequences in Staphylococcus carnosus and contribution of the enzyme to virulence. Infect. Immun. 57:29983002.
28. Goss, T. G.,, and R. A. Bender. Personal communication.
29. Grant, R. B.,, J. L. Penner,, J. N. Hennesey,, and B. J. Jackowski. 1981. Transferable urease activity in Providencia stuartii. J. Clin. Microbiol. 13:561565.
30. Grenbro, L.,, H. Hedelin,, and S. Petterson. 1988. Urinary infection stones caused by Ureaplasma urealyticum: a review. Scand. J. Infect. Dis. 53:4649.
31. Griffith, D. P.,, F. Khonsari,, J. H. Skurnick,, K. E. James,, and V. A. C. S. Group. 1988. A randomized trial of acetohydroxamic acid for the treatment and prevention of infection-induced urinary stones in spinal cord injury patients. J. Urol. 140:318324.
32. Griffith, D. P.,, D. M. Musher,, and C. Bin. 1976. Urease: the primary cause of infection-induced urinary stones. Invest. Urol. 13:346350.
33. Griffith, D. P.,, and C. A. Osborne. 1987. Infection (urease) stones. Min. Electrol. Metab. 13:278.
34. Hausinger, R. P. 1987. Nickel utilization by microorganisms. Microbiol. Rev. 51:2224.
35. Hawtin, P. R.,, A. R. Stacey,, and D. G. Newell. 1990. Investigation of the structure and location of the urease of Helicobacter pylori using monoclonal antibodies. J. Gen. Microbiol. 136:19952000.
36. Hazell, S. L.,, and A. Lee. 1986. Campylobacter pyloridis, urease, hydrogen ion back diffusion, and gastric ulcers. Lancet ii:1517.
37. Hu, L.,, and H. L. T. Mobley. 1990. Purification and N-terminal analysis of urease from Helicobacter pylori. Infect. Immun. 58:992998.
38. Hu, L.-T.,, P. A. Foxall,, R. Russell,, and H. L. T. Mobley. 1992. Purification of recombinant Helicobacter pylori urease apoenzyme encoded by ureA and ureB. Infect. Immun. 60:26572666.
39. Janssen, D. B.,, W. J. A. Habets,, J. T. Mamgg,, and C. van der Drift. 1982. Nitrogen control in Pseudomonas aeruginosa: mutants affected in the synthesis of glutamine synthetase, urease, and NADP-dependent glutamate dehydrogenase. J. Bacteriol. 151:2228.
40. Johnson, D. E.,, R. G. Russell,, C. V. Lockatell,, J. C. Zulty,, J. W. Warren,, and H. L. T. Mobley. 1993. Contribution of Proteus mirabilis urease to persistence, urolithiasis, and acute pyelonephritis in a mouse model of ascending urinary tract infection. Infect. Immun. 61:27482754.
41. Jones, B. D.,, C. V. Lockatell,, D. E. Johnson,, J. W. Warren,, and H. L. T. Mobley. 1990. Construction of a urease-negative mutant of Proteus mirabilis: analysis of virulence in a mouse model of ascending urinary tract infection. Infect. Immun. 58:11201123.
42. Jones, B. D.,, and H. L. T. Mobley. 1988. Proteus mirabilis urease: genetic organization, regulation, and expression of structural genes. J. Bacteriol. 170:33423349.
43. Jones, B. D.,, and H. L. T. Mobley. 1989. Proteus mirabilis urease: nucleotide sequence determination and comparison with jack bean urease. J. Bacteriol. 171:64146422.
44. Kenny, G. E.,, and F. D. Cartwright. 1977. Effect of urea concentration on growth of Ureaplasma urealyticum (T-strain mycoplasma). J. Bacteriol. 132:144150.
45. Labigne, A.,, V. Cussac,, and P. Courcoux. 1991. Shuttle cloning and nucleotide sequences of Helicobacter pylori genes responsible for urease activity. J. Bacteriol. 173:19201931.
46. Lee, M. H.,, S. B. Mulrooney,, and R. P. Hausinger. 1990. Purification, characterization, and in vivo recombination of Klebsiella aerogenes urease apoenzyme. J. Bacteriol. 172:44274431.
47. Lee, M. H.,, S. B. Mulrooney,, M. J. Renner,, Y. Markowicz,, and R. P. Hausinger. 1992. Klebsiella aerogenes urease gene cluster: sequence of ureD and demonstration that four accessory genes (ureD, ureE, ureF, ureG) are involved in nickel metallocenter biosynthesis. J. Bacteriol. 174:43244330.
48. Lee, M. H.,, H. S. Prankratz,, S. Wang,, R. A. Scott,, M. G. Finnegan,, M. K. Johnson,, J. A. Ippolito,, D. W. Christianson,, and R. P. Hausinger. 1993. Purification and characterization of Klebsiella aerogenes UreE protein: a nickel binding protein that functions in urease metallo center assembly. Prot. Sci. 2:10421052.
49. Lerner, S. P.,, M. J. Gleeson,, and D. P. Griffith. 1989. Infection stones. J. Urol. 141:753758.
50. Macaluso, A.,, E. A. Best,, and R. A. Bender. 1990. Role of the nac gene product in the nitrogen regulation of some NTR-regulated operons of Klebsiella aerogenes. J. Bacteriol. 172:72497255.
51. MacLaren, D. M.,, and P. G. H. Peerbooms,. 1986. Urinary infections by urea splitting microorganisms. In A. W. Brumfit (ed.), Microbial Diseases in Nephrology. John Wiley & Sons, New York.
52. Maeda, M.,, M. Hidaka,, A. Nakamura,, H. Masaki,, and T. Uozumi. 1994. Cloning, sequencing, and expression of the thermophilic Bacillus sp. strain TB-90 urease gene complex in Escherichia coli. J. Bacteriol. 176:432442.
53. Magasanik, B.,, and F. C. Neidhardt,. 1987. Regulation of carbon and nitrogen utilization, p. 13181325. In F. C. Neidhardt,, J. L. Ingraham,, K. B. Low,, B. Magasanik,, M. Schaechter,, and H. E. Umbarger (ed.), Escherichia coli and Salmonella typhimurium: Cellular and Molecular Biology. American Society for Microbiology, Washington D.C..
54. Mai, U. E. H.,, G. I. Perez-Perez,, J. B. Allen,, S. M. Wahl,, M. J. Blaser,, and P. D. Smith. 1992. Surface proteins from Helicobacter pylori exhibit chemotactic activity for human leukocytes and are present in gastric mucosa. J. Exp. Med. 175:517525.
55. Maier, T.,, A. Jacob),, M. Sauter,, and A. Hock. 1993. The product of the hypB gene, which is required for nickel incorporation into hydrogenases, is a novel guanine nucleotide-binding protein. J. Bacteriol. 175:630635.
56. Marshall, B. J.,, L. Barret,, C. Prakesh,, R. McCallum,, and R. Guerrant,. 1988. Protection of Campylobacter pyloridis but not Campylobacter jejuni against acid susceptibility by urea, p. 402403. In B. Kaijserand, E. Falsen (ed.), Campylobacter IV. University of Goteborg, Goteborg, Sweden.
57. McLean, R. J. C.,, J. C. Nickel,, K.-J. Cheng,, and J. W. Costerton. 1988. The ecology and pathogenicity of urease-producing bacteria in the urinary tract. Crit. Rev. Microbiol. 16:3779.
58. Mertz, A.,, S. Batsford,, E. Curschellas,, M. Kist,, and K. Gondolf. 1991. Cationic Yersinia antigen-induced chronic allergic arthritis in rats. J. Clin. Invest. 88:632642.
59. Milkier, O. E. J.,, J. A. Andersen,, M. E. Appier,, C. E. Benjamin,, J. G. Edwards,, D. T. Humphrey,, and E. M. Shearer. 1982. Flurofamide: a potential inhibitor of bacterial urease with a potential clinical utility in the treatment of infection induced urinary stones. J. Urol. 127:346350.
60. Mobley, H. L. T.,, G. R. Chippendale,, M. H. Fraiman,, J. H. Tenney,, and J. W. Warren. 1985. Variable phenotypes of Providencia stuartii due to plasmid-encoded traits. J. Clin. Microbiol. 22: 851853.
61. Mobley, H. L. T.,, G. R. Chippendale,, K. G. Swihart,, and R. A. Welch. 1991. Cytotoxicity of the HmpA hemolysis and urease of Proteus mirabilis and Proteus vulgaris against cultured human renal proximal tubular epithelial cells. Infect. Immun. 59:20362042.
62. Mobley, H. L. T.,, and R. P. Hausinger. 1989. Microbial ureases: significance, regulation, and molecular characterization. Microbiol. Rev. 53:85108.
63. Mobley, H. L. T.,, B. D. Jones,, and A. E. Jerse. 1986. Cloning of urease gene sequences from Providencia stuartii. Infect. Immun. 54:161169.
64. Mobley, H. L. T.,, and J. W. Warren. 1987. Urease-positive bacteriuria and obstruction of long-term urinary catheters. J. Clin. Microbiol. 25:22162217.
65. Mulrooney, S. B.,, and R. P. Hausinger. 1990. Sequence of the Klebsiella aerogenes urease genes and evidence for accessory proteins facilitating nickel incorporation. J. Bacteriol. 172:58375843.
66. Mulrooney, S. B.,, M. J. Lynch,, H. L. T. Mobley,, and R. P. Hausinger. 1988. Purification, characterization, and genetic organization of recombinant Providencia stuartii urease expressed by Escherichia coli. J. Bacteriol. 170:22022207.
67. Musher, D. M.,, D. P. Griffith,, D. Yawn,, and R. D. Rossen. 1975. Role of urease in pyelonephritis resulting from urinary tract infection with Proteus. J. Infect. Dis. 131:177181.
68. Needleman, S. B.,, and C. D. Wunsch. 1970. A general method applicable to the search for similarity in the amino acid sequence of two proteins. J. Mol. Biol. 48:443453.
69. Nicholson, E. B.,, E. A. Concaugh,, P. A. Foxall,, M. D. Island,, and H. L. T. Mobley. 1993. Proteus mirabilis urease: transcriptional regulation by UreR. J. Bacteriol. 175:465473.
70. Nicholson, E. B.,, E. A. Concaugh,, and H. L. T. Mobley. 1991. Proteus mirabilis urease: use of a ureA-lacZ fusion demonstrates that induction is highly specific for urea. J. Bacteriol. 59: 33603365.
71. Nomura, A.,, G. N. Stemmermann,, P.-H. Chyou,, I. Kato,, G. I. Perez-Perez,, and M. J. Blaser. 1991. Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N. Engl. J. Med. 325:11321136.
72. Parsonnet, J.,, G. D. Friedman,, D. P. Vandersteen,, Y. Chang,, J. H. Vogelman,, N. Orentreich,, and R. K. Sibley. 1991. Helicobacter pylori infection and the risk of gastric carcinoma. N. Engl. J. Med. 325:11211131.
73. Pickering, W. J.,, and D. F. Birch. 1989. Bacteriologic and serologic findings in experimental pyelonephritis caused by Ureaplasma urealyticum. Infect. Immun. 57:12351239.
74. Probst, P.,, E. Hermann,, K.-H. Meyer zum Buschenfelde,, and B. Fleischer. 1993. Identification of the Yersinia enterocolitica urease B subunit as a target antigen for human synovial T lymphocytes in reactive arthritis. Infect. Immun. 61:45074509.
75. Przybyla, A. E.,, J. Robbins,, N. Menon,, and H. D. J. Peck. 1992. Structure/function relationships among the nickel-containing hydrogenases. FEMS Microbiol. Rev. 88:109136.
76. Romano, N.,, R. La Litica,, and D. R. Alesi. 1986. Energy production in Ureaplasma urealyticum. Pediatr. Infect. Dis. J. 5:S308S312.
77. Rosenstein, I.,, J. M. T. Hamilton-Miller,, and W. Brumfit. 1980. The effect of acetohydroxamic acids on the induction of bacterial ureases. Invest. Urol. 18:112114.
78. Schwada, A.,, and R. A. Bender. 1993. The nac (nitrogen assimilation control) gene from Klebsiella aerogenes. J. Bacteriol. 175:21072115.
79. Segal, E. D.,, J. Shon,, and L. S. Tompkins. 1992. Characterization of Helicobacter pylori urease mutants. Infect. Immun. 60:18831889.
80. Senior, B. W. 1983. Proteus morganii is less frequently associated with urinary tract infections than Proteus mirabilis—an explanation. J. Med. Microbiol. 16:317322.
81. Sheath, P. H. A.,, and R. R. Sokal. 1973. Numerical Taxonomy. W. H. Freeman & Co., San Francisco.
82. Sizer, I. W. 1941. Temperature activation of the urease-urea system using urease of Proteus vulgaris. J. Bacteriol. 41:511527.
83. Skurnik, M.,, S. Batsford,, A. Mertz,, E. Schiltz,, and P. Toivanen. 1993. The putative arthritogenic cationic 19-kilodalton antigen of Yersinia enterocolitica is a urease β subunit. Infect. Immun. 61: 24982504.
84. Smoot, D. T.,, H. L. T. Mobley,, G. R. Chippendale,, J. F. Lewison,, and J. H. Resau. 1990. Helicobacter pylori urease activity is toxic to human gastric epithelial cells. Infect. Immun. 58:19921994.
85. Stetnke, G. W.,, J. A. Robertson,, and M. Nhan. 1987. Purification of urease from Ureaplasma urealyticum. Can. J. Microbiol. 33:857862.
86. Suzuki, M.,, S. Miura,, M. Suematsu,, D. Fukumura,, I. Kurose,, H. Suzuki,, A. Kai,, Y. Kudoh,, M. Ohashi,, and M. Tsuchiya. 1992. Helicobacter pylori-associated ammonia production enhances neutrophil-dependent gastric mucosal cell injury. Am. J. Physiol. 263:G719G725.
87. Takebe, S.,, A. Numata,, and K. Kobashi. 1984. Stone formation by Ureaplasma urealyticum in human urine and its prevention by urease inhibitors. J. Clin. Microbiol. 20:869873.
88. Takeuchi, H.,, K. Kobashi,, and O. Yoshida. 1980. Prevention of infected urinary stones in rats by urease inhibitor. Invest. Urol. 18:102105.
89. Thirkell, D.,, A. D. Myles,, B. L. Precious,, J. S. Frost,, J. C. Woodall,, M. G. Burdon,, and W. C. Russell. 1989. The urease of Ureaplasma urealyticum. J. Gen. Microbiol. 135:315323.
90. Todd, M. J.,, and R. P. Hausinger. 1987. Purification and characterization of the nickel-containing multicomponent urease fron Klebsiella aerogenes. J. Biol. Chem. 262:59635967.
91. Totten, P. A.,, J. C. Lara,, and S. Lory. 1990. The rpoN gene product of Pseudomonas aeruginosa is required for expression of diverse genes, including the flagellin gene. J. Bacteriol. 172:389396.


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Table 1

Urease gene transcriptional activators

Citation: Collins C. 1994. The Tao of Urease, p 437-449. In Miller V, Kaper J, Portnoy D, Isberg R (ed), Molecular Genetics of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818340.ch29

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