Increased Incidence of Urolithiasis and Bacteremia During Proteus Mirabilis and Providencia Stuartii Coinfection Due to Synergistic Induction of Urease Activity

J Infect Dis. 2014 May 15;209(10):1524-32. doi: 10.1093/infdis/jit663. Epub 2013 Nov 26.


Background: Catheter-associated urinary tract infections (CaUTIs) are the most common hospital-acquired infections worldwide and are frequently polymicrobial. The urease-positive species Proteus mirabilis and Providencia stuartii are two of the leading causes of CaUTIs and commonly co-colonize catheters. These species can also cause urolithiasis and bacteremia. However, the impact of coinfection on these complications has never been addressed experimentally.

Methods: A mouse model of ascending UTI was utilized to determine the impact of coinfection on colonization, urolithiasis, and bacteremia. Mice were infected with P. mirabilis or a urease mutant, P. stuartii, or a combination of these organisms. In vitro experiments were conducted to assess growth dynamics and impact of co-culture on urease activity.

Results: Coinfection resulted in a bacterial load similar to monospecies infection but with increased incidence of urolithiasis and bacteremia. These complications were urease-dependent as they were not observed during coinfection with a P. mirabilis urease mutant. Furthermore, total urease activity was increased during co-culture.

Conclusions: We conclude that P. mirabilis and P. stuartii coinfection promotes urolithiasis and bacteremia in a urease-dependent manner, at least in part through synergistic induction of urease activity. These data provide a possible explanation for the high incidence of bacteremia resulting from polymicrobial CaUTI.

Keywords: Proteus mirabilis; Providencia stuartii; UTI; bacteremia; coinfection; urease; urolithiasis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacteremia / microbiology*
  • Coinfection*
  • Enterobacteriaceae Infections / complications*
  • Enterobacteriaceae Infections / microbiology
  • Enzyme Induction
  • Gene Expression Regulation, Bacterial / physiology
  • Mice
  • Mice, Inbred CBA
  • Proteus Infections / complications
  • Proteus Infections / microbiology
  • Proteus mirabilis*
  • Providencia*
  • Urease / metabolism
  • Urolithiasis / microbiology*


  • Urease