: Urinary tract infections (UTIs) are one of the most frequently diagnosed kidney and urological disorders. While Proteus mirabilis is responsible for only a few percent of all UTIs, individuals with anatomical abnormalities or long-term indwelling medical devices are highly susceptible to P. mirabilis bladder and kidney infections. A hallmark of P. mirabilis UTI is the formation of bladder and kidney stones due to the urea-induced activity of urease. Ammonia formed by the urease-catalyzed breakdown of urea increases local pH resulting in crystallization of magnesium and calcium metal salts. Urease statement is regulated by UreR, a member of the AraC family of transcriptional regulators. UreR DNA-binding properties and transcriptional activity have been partially characterized. We hypothesize that urea binds directly to UreR resulting in a conformational change in the protein which alters its interaction DNA. Purified recombinant UreR will be used to study the effect of urea and DNA on UreR dimerization. Equilibrium dialysis will be used to measure the urea binding constant for UreR. In the absence of urea, we hypothesize that UreR stimulates DNA looping which shuts off transcription of urease. The ability of UreR to induce bends in DNA will be evaluated using circular permutation analysis. Further work will be performed using DNA minicircles containing UreR binding sites. We will determine if an inverted UreR dimer is formed in the presence and absence of urea. This research will be used to develop a model for the UreR-mediated transcription regulation of the urease operon.
| Dattelbaum, Jonathan D; Lockatell, C Virginia; Johnson, David E et al. (2003) UreR, the transcriptional activator of the Proteus mirabilis urease gene cluster, is required for urease activity and virulence in experimental urinary tract infections. Infect Immun 71:1026-30 |
