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Urinary catheter use is prevalent in health care settings, and polymicrobial colonization by urease-positive organisms, such asProteus mirabilis andProvidencia stuartii , commonly occurs with long-term catheterization. We previously demonstrated that coinfection withP. mirabilis andP. stuartii increased overall urease activityin 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 ofP. stuartii , regardless of urease production by this organism, was sufficient to enhanceP. 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 enhancedP. mirabilis urease activityin vitro , including recent clinical isolates ofEscherichia coli ,Enterococcus faecalis ,Klebsiella pneumoniae , andPseudomonas 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 byP. mirabilis and other urease-positive bacteria.

The Pathogenic Potential of Proteus mirabilis Is Enhanced by Other Uropathogens during Polymicrobial Urinary Tract Infection