title: The Pathogenic Potential of Proteus mirabilis Is Enhanced by Other Uropathogens during Polymicrobial Urinary Tract Infection.
abstract: Urinary catheter use is prevalent in health care settings, and polymicrobial colonization by urease-positive organisms, such as Proteus mirabilis and Providencia stuartii, commonly occurs with long-term catheterization. We previously demonstrated that coinfection with P. mirabilis and P. stuartii increased overall urease activity in vitro and disease severity in a model of urinary tract infection (UTI). In this study, we expanded these findings to a murine model of catheter-associated UTI (CAUTI), delineated the contribution of enhanced urease activity to coinfection pathogenesis, and screened for enhanced urease activity with other common CAUTI pathogens. In the UTI model, mice coinfected with the two species exhibited higher urine pH values, urolithiasis, bacteremia, and more pronounced tissue damage and inflammation compared to the findings for mice infected with a single species, despite having a similar bacterial burden within the urinary tract. The presence of P. stuartii, regardless of urease production by this organism, was sufficient to enhance P. mirabilis urease activity and increase disease severity, and enhanced urease activity was the predominant factor driving tissue damage and the dissemination of both organisms to the bloodstream during coinfection. These findings were largely recapitulated in the CAUTI model. Other uropathogens also enhanced P. mirabilis urease activity in vitro, including recent clinical isolates of Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, and Pseudomonas aeruginosa We therefore conclude that the underlying mechanism of enhanced urease activity may represent a widespread target for limiting the detrimental consequences of polymicrobial catheter colonization, particularly by P. mirabilis and other urease-positive bacteria.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA chelarmb@umich.edu hmobley@umich.edu.
authors.forename: Chelsie E
authors.initials: CE
authors.lastname: Armbruster
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Sara N
authors.initials: SN
authors.lastname: Smith
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Alexandra O
authors.initials: AO
authors.lastname: Johnson
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Valerie
authors.initials: V
authors.lastname: DeOrnellas
authors.affiliation: Laboratory Animal Medicine Unit, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Eaton
authors.affiliation: Biological Sciences Department, California Polytechnic State University, San Luis Obispo, California, USA.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Yep
authors.affiliation: Division of Geriatric and Palliative Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.|Geriatrics Research Education and Clinical Center, VA Ann Arbor Healthcare System, Ann Arbor, Michigan, USA.
authors.forename: Lona
authors.initials: L
authors.lastname: Mody
authors.affiliation: Department of Computational Medicine & Bioinformatics, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Weisheng
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA chelarmb@umich.edu hmobley@umich.edu.
authors.forename: Harry L T
authors.initials: HLT
authors.lastname: Mobley
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000382:microbiology; D058491:Bacterial Load; D060085:Coinfection; D004195:Disease Models, Animal; D005260:Female; D016680:Genome, Bacterial; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D009154:Mutation; D011513:Proteus mirabilis / Q000145:classification / Q000201:enzymology / Q000235:genetics; D013559:Symbiosis; D014510:Urease / Q000378:metabolism; D014546:Urinary Catheterization / Q000009:adverse effects; D014552:Urinary Tract Infections / Q000382:microbiology* / Q000473:pathology; D052878:Urolithiasis / Q000209:etiology
chemical_list: D014510:Urease
keywords: CAUTI; Enterococcus; Proteus mirabilis; Providencia stuartii; UTI; catheter-associated urinary tract infection; polymicrobial; urease; urinary tract infection