Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.3.4.6 (urease)
 7,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteus mirabilis, a cause of complicated urinary tract infection, produces urease, an essential virulence factor for this species. UreR, a member of the AraC/XylS family of transcriptional regulators, positively activates expression of the ure gene cluster in the presence of urea. To specifically evaluate the contribution of UreR to urease activity and virulence in the urinary tract, a ureR mutation was introduced into P. mirabilis HI4320 by homologous recombination. The isogenic ureR::aphA mutant, deficient in UreR production, lacked measurable urease activity. Expression was not detected in the UreR-deficient strain by Western blotting with monoclonal antibodies raised against UreD. Urease activity and UreD expression were restored by complementation of the mutant strain with ureR expressed from a low-copy-number plasmid. Virulence was assessed by transurethral cochallenge of CBA mice with wild-type and mutant strains. The isogenic ureR::aphA mutant of HI4320 was outcompeted in the urine (P = 0.004), bladder (P = 0.016), and kidneys (P < or = 0.001) 7 days after inoculation. Thus, UreR is required for basal urease activity in the absence of urea, for induction of urease by urea, and for virulence of P. mirabilis in the urinary tract.
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PMID:UreR, the transcriptional activator of the Proteus mirabilis urease gene cluster, is required for urease activity and virulence in experimental urinary tract infections. 1254 May 89

Proteus mirabilis, a cause of catheter-associated urinary tract infection, relies on several virulence factors to colonize the urinary tract. Among these, urease contributes to the development of urinary stones resulting from the increase in local pH due to urease-mediated hydrolysis of urea to NH(3) and CO(2). UreR, an AraC-like transcriptional activator, activates transcription of the genes encoding the urease subunits and accessory proteins (ureDABCEFG) in the presence of urea. UreR also initiates transcription of its own gene in a urea-inducible manner by binding to the intergenic region between ureR and ureD. The intergenic region contains poly(A) tracts that appear to be the target of H-NS. It has been shown that Escherichia coli and P. mirabilis H-NS acts to repress transcription of ureR in an E. coli model system. It was hypothesized that H-NS represses urease gene expression in the absence of UreR and urea by binding to the intergenic region. To demonstrate this the P. mirabilis hns gene was cloned and the 15.6 kDa H-NS was overexpressed and purified as a myc-His tail fusion. Using a gel shift assay, purified H-NS-myc-His bound preferentially to a 609 bp DNA fragment containing the entire ureR-ureD intergenic region. H-NS and UreR were able to displace each other from the ureR-ureD intergenic region. Circular permutation analysis revealed that the intergenic region is bent. Moreover, H-NS recognizes this curvature, binds the DNA fragment and induces further bending of the DNA as shown by a circular ligation assay. The effects of H-NS, urea and temperature (25 vs 37 degrees C) on urease expression were shown in E. coli containing an hns knockout and P. mirabilis where expression was increased at 37 degrees C. Increased transcription from p(ureR) was seen in the E. coli hns knockout when temperature was increased from 25 to 37 degrees C. These findings suggest H-NS and UreR differentially regulate urease in a negative and positive manner, respectively.
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PMID:Differential regulation of the Proteus mirabilis urease gene cluster by UreR and H-NS. 1466 72

The Escherichia coli plasmid-encoded urease, a virulence factor in human and animal infections of the urinary and gastroduodenal tracts, is induced when the substrate urea is present in the growth medium. Urea-dependent urease expression is mediated at the transcriptional level by the AraC-like activator UreR. Previous work has shown that a peptide representing the N-terminal 194 amino-acid residues of UreR binds urea at a single site, full-length UreR forms an oligomer, and the oligomerization motif is thought to reside in the N-terminal portion of the molecule. The C-terminal domain of UreR contains two helix-turn-helix motifs presumed to be necessary for DNA binding. In this study, we exploited mutational analyses at the N-terminal domain of UreR to determine if this domain dimerizes similar to other AraC family members. UreR mutants were analyzed for the ability to activate transcription of lacZ from an ureDp-lacZ transcriptional fusion. A construct encoding the N-terminal 194 amino acids of UreR, eluted as an oligomer by gel filtration and had a dominant negative phenotype over the wild-type ureR allele. We hypothesize that this dominant negative phenotype results from the formation of inactive heterodimers between wild-type and truncated UreR. Dominant negative analysis and cross-linking assays demonstrated that E. coli UreR is active as a dimer and dimerization occurs within the first 180 residues.
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PMID:Mutational analysis of the N-terminal domain of UreR, the positive transcriptional regulator of urease gene expression. 2253 74


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