Academic Journal
Staphylococcus aureus urease is controlled by a complex regulatory network to promote dissemination during CAUTI.
| Τίτλος: | Staphylococcus aureus urease is controlled by a complex regulatory network to promote dissemination during CAUTI. |
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| Συγγραφείς: | Gomez J; Department of Microbiology and Molecular Genetics, McGovern Medical School, Houston, Texas, USA.; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, Texas, USA., Duran-Ramirez J; Department of Microbiology and Molecular Genetics, McGovern Medical School, Houston, Texas, USA.; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, Texas, USA., Alvarez M; Department of Microbiology and Molecular Genetics, McGovern Medical School, Houston, Texas, USA., Cristy S; Department of Microbiology and Molecular Genetics, McGovern Medical School, Houston, Texas, USA.; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, Texas, USA., Walker JN; Department of Microbiology and Molecular Genetics, McGovern Medical School, Houston, Texas, USA.; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, Texas, USA.; Center for Infectious Diseases, Department of Epidemiology, UTHealth School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, USA. |
| Πηγή: | MBio [mBio] 2026 Sep 09; Vol. 17 (9), pp. e0162426. Date of Electronic Publication: 2026 Aug 05. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, D.C. : American Society for Microbiology |
| Ιατρικοί όροι (MeSH): | Urease*/genetics , Urease*/metabolism , Staphylococcus aureus*/enzymology , Staphylococcus aureus*/genetics , Staphylococcus aureus*/pathogenicity , Staphylococcus aureus*/growth & development , Catheter-Related Infections*/microbiology , Staphylococcal Infections*/microbiology , Urinary Tract Infections*/microbiology , Gene Expression Regulation, Bacterial* , Gene Regulatory Networks*, Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Virulence Factors/genetics ; Animals ; Mice ; Humans |
| Περίληψη: | Catheter-associated urinary tract infections (CAUTIs) are one of the most common hospital-associated infections in the United States, accounting for >1 million cases annually. One CAUTI pathogen, Staphylococcus aureus, is commonly found persisting asymptomatically in the bladder of catheterized individuals, increasing these individuals' risk of developing infection. Importantly, S. aureus is not only associated with severe symptoms during CAUTI, including bacteremia and septic shock, but it also produces a common uropathogen-associated virulence factor, urease. Despite its importance, urease has only been well-studied in another uropathogen, Proteus mirabilis. While previous studies identified three S. aureus urease regulators, including CodY, CcpA, and Agr, the environmental signals required for expression and activity, and the enzyme's contribution to CAUTI have not been explored. In this study, we demonstrate that post-exponential growth and growth in the urinary tract environment significantly induce S. aureus urease expression and activity. Additionally, we identify SigB, SaeR, and SrrA as novel regulators of urease, and further explore the role of CodY, CcpA, and Agr-previously implicated in urease expression-in urease regulation in the urinary tract environment. Impactfully, we found that the urease promoters of clinical isolates contain genomic changes that enhance urease expression. Furthermore, urease contributes to biofilm formation under catheterized urinary tract-like conditions in vitro and dissemination from the bladder to the kidneys in a mouse CAUTI model. Together, our data not only provide insight into the regulatory pathway controlling S. aureus urease but also emphasize the importance of studying these mechanisms in a model that mimics the urinary environment. Importance: In this study, we investigate how regulatory pathways coordinate the expression and activity of urease in response to environmental signals present within the catheterized urinary tract. We show that growth during the post-exponential phase and in conditions that mimic the urinary tract increases urease expression and activity. This finding challenges the dogma that Staphylococcus aureus is a "weak" urease producer. We also identified three novel regulators of S. aureus urease-SigB, SrrA, and SaeR-and show that their respective activation signals can modulate urease expression. Additionally, single-nucleotide changes identified in the urease regulatory pathway of clinical urinary catheter-associated isolates enhance urease expression. Finally, urease promotes biofilm formation under conditions that mimic the catheterized urinary tract and dissemination during catheter-associated urinary tract infections (CAUTIs). Our study provides insight into the complex regulatory mechanisms controlling urease in the urinary tract and highlights the role urease plays in S. aureus CAUTI. |
| Competing Interests: | The authors declare no conflict of interest. |
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| Grant Information: | K01 DK128381 United States DK NIDDK NIH HHS; 25PRE1372661 American Heart Association; K01 DK128381-01A1 United States DK NIDDK NIH HHS |
| Contributed Indexing: | Keywords: Staphylococcus aureus; catheter-associated urinary tract infections; gene regulation; urease |
| Substance Nomenclature: | EC 3.5.1.5 (Urease) 0 (Bacterial Proteins) 0 (Virulence Factors) |
| Entry Date(s): | Date Created: 20260805 Date Completed: 20260909 Latest Revision: 20260912 |
| Update Code: | 20260912 |
| PubMed Central ID: | PMC13556217 |
| DOI: | 10.1128/mbio.01624-26 |
| PMID: | 42554478 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2150-7511 |
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| DOI: | 10.1128/mbio.01624-26 |