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Hot Biological Catalysis: Isothermal Titration Calorimetry to Characterize Enzymatic Reactions
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Proteus mirabilis UreR coordinates cellular functions required for urease activity
Madison J Fitzgerald1, Melanie M Pearson1, Harry L T Mobley1
1Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Journal of Bacteriology
|March 27, 2024
Summary
Proteus mirabilis urease, essential for urinary stone formation, is regulated by UreR. This study reveals UreR controls nickel transport, crucial for mature urease production and virulence in urinary tract infections.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Proteus mirabilis causes urinary tract infections (UTIs) and kidney stones via urease activity.
- Urease requires nickel for maturation, and its expression is regulated by UreR.
- Catheter-associated UTIs (CAUTIs) are a significant healthcare burden, with P. mirabilis as a key pathogen.
Purpose of the Study:
- To define the P. mirabilis urea-induced transcriptome and the UreR regulon.
- To investigate UreR's role in regulating urease gene expression and nickel transport.
- To explore the conservation of UreR-mediated regulation in related species.
Main Methods:
- Comprehensive RNA-sequencing (RNA-seq) to analyze gene expression.
- Bioinformatic analysis to identify UreR-regulated genes and conserved loci.
- Investigating nickel transport regulation by UreR.
Main Results:
- UreR regulates genes essential for mature urease production, including nickel transport.
- UreR is identified as the first regulator of nickel transport in P. mirabilis.
- Conserved UreR-regulated urease and nickel transporter loci were found in 15 Morganellaceae species.
Conclusions:
- UreR plays a critical role in P. mirabilis uropathogenesis by regulating urease production and nickel import.
- The regulation of nickel transport by UreR is a conserved mechanism in the Morganellaceae family.
- Understanding UreR's regulatory network provides insights into P. mirabilis virulence and potential therapeutic targets.
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