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Staphylococcus aureus urease is controlled by a complex regulatory network to promote dissemination during CAUTI.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Staphylococcus aureus urease is controlled by a complex regulatory network to promote dissemination during CAUTI.
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
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  Data: Staphylococcus aureus urease is controlled by a complex regulatory network to promote dissemination during CAUTI.
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  Data: <searchLink fieldCode="AU" term="%22Gomez+J%22">Gomez J</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Duran-Ramirez+J%22">Duran-Ramirez J</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Alvarez+M%22">Alvarez M</searchLink>; Department of Microbiology and Molecular Genetics, McGovern Medical School, Houston, Texas, USA.<br /><searchLink fieldCode="AU" term="%22Cristy+S%22">Cristy S</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Walker+JN%22">Walker JN</searchLink>; 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.
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  Data: <i>Original Publication</i>: Washington, D.C. : American Society for Microbiology
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  Data: <searchLink fieldCode="MM" term="%22Urease%22">Urease*</searchLink>/<searchLink fieldCode="MM" term="%22Urease+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Urease%22">Urease*</searchLink>/<searchLink fieldCode="MM" term="%22Urease+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Staphylococcus+aureus%22">Staphylococcus aureus*</searchLink>/<searchLink fieldCode="MM" term="%22Staphylococcus+aureus+enzymology%22">enzymology</searchLink> <br /><searchLink fieldCode="MM" term="%22Staphylococcus+aureus%22">Staphylococcus aureus*</searchLink>/<searchLink fieldCode="MM" term="%22Staphylococcus+aureus+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Staphylococcus+aureus%22">Staphylococcus aureus*</searchLink>/<searchLink fieldCode="MM" term="%22Staphylococcus+aureus+pathogenicity%22">pathogenicity</searchLink> <br /><searchLink fieldCode="MM" term="%22Staphylococcus+aureus%22">Staphylococcus aureus*</searchLink>/<searchLink fieldCode="MM" term="%22Staphylococcus+aureus+growth+%26+development%22">growth & development</searchLink> <br /><searchLink fieldCode="MM" term="%22Catheter-Related+Infections%22">Catheter-Related Infections*</searchLink>/<searchLink fieldCode="MM" term="%22Catheter-Related+Infections+microbiology%22">microbiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Staphylococcal+Infections%22">Staphylococcal Infections*</searchLink>/<searchLink fieldCode="MM" term="%22Staphylococcal+Infections+microbiology%22">microbiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Urinary+Tract+Infections%22">Urinary Tract Infections*</searchLink>/<searchLink fieldCode="MM" term="%22Urinary+Tract+Infections+microbiology%22">microbiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Gene+Expression+Regulation%2C+Bacterial%22">Gene Expression Regulation, Bacterial*</searchLink> <br /><searchLink fieldCode="MM" term="%22Gene+Regulatory+Networks%22">Gene Regulatory Networks*</searchLink><br /><searchLink fieldCode="MH" term="%22Bacterial+Proteins%22">Bacterial Proteins</searchLink>/<searchLink fieldCode="MH" term="%22Bacterial+Proteins+genetics%22">genetics</searchLink> ; <searchLink fieldCode="MH" term="%22Bacterial+Proteins%22">Bacterial Proteins</searchLink>/<searchLink fieldCode="MH" term="%22Bacterial+Proteins+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Virulence+Factors%22">Virulence Factors</searchLink>/<searchLink fieldCode="MH" term="%22Virulence+Factors+genetics%22">genetics</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Mice%22">Mice</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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.<br />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.
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: The authors declare no conflict of interest.
– Name: Ref
  Label: References
  Group: RefInfo
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(PMID: <searchLink fieldCode="PM" term="%2226827873%22">26827873)</searchLink><br />J Bacteriol. 2010 Apr;192(8):2111-27. (PMID: <searchLink fieldCode="PM" term="%2220172998%22">20172998)</searchLink><br />Proc Natl Acad Sci U S A. 2017 Oct 10;114(41):E8721-E8730. (PMID: <searchLink fieldCode="PM" term="%2228973850%22">28973850)</searchLink><br />Front Cell Infect Microbiol. 2022 Mar 22;12:859093. (PMID: <searchLink fieldCode="PM" term="%2235392611%22">35392611)</searchLink><br />Microbiol Spectr. 2015 Oct;3(5):. (PMID: <searchLink fieldCode="PM" term="%2226542046%22">26542046)</searchLink><br />mBio. 2013 Nov 12;4(6):e00696-13. (PMID: <searchLink fieldCode="PM" term="%2224222487%22">24222487)</searchLink><br />Scand J Infect Dis. 2013 Sep;45(9):688-95. (PMID: <searchLink fieldCode="PM" term="%2223808717%22">23808717)</searchLink><br />J Bacteriol. 2000 Jun;182(11):3197-203. 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  Data: K01 DK128381 United States DK NIDDK NIH HHS; 25PRE1372661 American Heart Association; K01 DK128381-01A1 United States DK NIDDK NIH HHS
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  Data: <i>Keywords: </i>Staphylococcus aureus; catheter-associated urinary tract infections; gene regulation; urease
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  Data: EC 3.5.1.5 (Urease)<br />0 (Bacterial Proteins)<br />0 (Virulence Factors)
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        Value: 10.1128/mbio.01624-26
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      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: e0162426
    Subjects:
      – SubjectFull: Bacterial Proteins genetics
        Type: general
      – SubjectFull: Bacterial Proteins metabolism
        Type: general
      – SubjectFull: Virulence Factors genetics
        Type: general
      – SubjectFull: Animals
        Type: general
      – SubjectFull: Mice
        Type: general
      – SubjectFull: Humans
        Type: general
      – SubjectFull: Urease genetics
        Type: general
      – SubjectFull: Urease metabolism
        Type: general
      – SubjectFull: Staphylococcus aureus enzymology
        Type: general
      – SubjectFull: Staphylococcus aureus genetics
        Type: general
      – SubjectFull: Staphylococcus aureus pathogenicity
        Type: general
      – SubjectFull: Staphylococcus aureus growth & development
        Type: general
      – SubjectFull: Catheter-Related Infections microbiology
        Type: general
      – SubjectFull: Staphylococcal Infections microbiology
        Type: general
      – SubjectFull: Urinary Tract Infections microbiology
        Type: general
      – SubjectFull: Gene Expression Regulation, Bacterial
        Type: general
      – SubjectFull: Gene Regulatory Networks
        Type: general
    Titles:
      – TitleFull: Staphylococcus aureus urease is controlled by a complex regulatory network to promote dissemination during CAUTI.
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            – D: 09
              M: 09
              Text: 2026 Sep 09
              Type: published
              Y: 2026
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