Proteus mirabilis UreR coordinates cellular functions required for urease activity

• DOI: 10.1128/jb.00031-24
• Publication Date: 2024-03-27T13:02:49Z
• Authors: Madison J. Fitzge...; Melanie M. Pearson; Harry L. T. Mobley
• Keywords: 0301 basic medicine; Urease; Mice; 03 medical and health sciences; Bacterial Proteins; Nickel; Urinary Tract Infections; Escherichia coli; Animals; Urea; Proteus Infections; Proteus mirabilis

ABSTRACT A hallmark of Proteus mirabilis infection the urinary tract is formation stones. The ability to induce stone requires urease, a nickel metalloenzyme that hydrolyzes urea. This reaction produces ammonia as byproduct, which can serve nitrogen source and weak base raises local pH. resulting alkalinity induces precipitation ions form Transcriptional regulator UreR activates expression urease genes in urea-dependent manner. Thus, are highly expressed where urea abundant. Production mature also import into cytoplasm its incorporation apoenzyme. Urease accessory proteins primarily acquire from one two transporters facilitate urease. In this study, we performed comprehensive RNA-seq define P. urea-induced transcriptome well regulon. We identified first defined transport . offer evidence for direct regulation Ynt transporter by UreR. Using bioinformatics, UreR-regulated loci 15 Morganellaceae family species across three genera. Additionally, located mobilized encode ynt transporter, implying conserved regulatory relationship. Our study demonstrates specifically regulates required produce an essential virulence factor uropathogenesis. IMPORTANCE Catheter-associated infections (CAUTIs) account over 40% acute nosocomial USA generate $340 million healthcare costs annually. major causative agent CAUTIs , understudied Gram-negative pathogen noted stones via activity mutants cannot attenuated murine UTI model, indicating enzyme pathogenesis. established; here, expand regulon include import, function Furthermore, reflect on role catalysis metabolism provide importance.