title: Increased incidence of urolithiasis and bacteremia during Proteus mirabilis and Providencia stuartii coinfection due to synergistic induction of urease activity.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Chelsie E
authors.initials: CE
authors.lastname: Armbruster
authors.forename: Sara N
authors.initials: SN
authors.lastname: Smith
authors.forename: Alejandra
authors.initials: A
authors.lastname: Yep
authors.forename: Harry L T
authors.initials: HL
authors.lastname: Mobley
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000382:microbiology*; D060085:Coinfection; D004756:Enterobacteriaceae Infections / Q000150:complications* / Q000382:microbiology; D004790:Enzyme Induction; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D051379:Mice; D008808:Mice, Inbred CBA; D011512:Proteus Infections / Q000150:complications / Q000382:microbiology; D011513:Proteus mirabilis; D011532:Providencia; D014510:Urease / Q000378:metabolism; D052878:Urolithiasis / Q000382:microbiology*
chemical_list: D014510:Urease
keywords: Proteus mirabilis; Providencia stuartii; UTI; bacteremia; coinfection; urease; urolithiasis