Fibrinolytic-deficiencies predispose hosts to septicemia from a catheter-associated UTI

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Abstract
Catheter-associated urinary tract infections (CAUTIs) are amongst the most common nosocomial infections worldwide and are difficult to treat partly due to development of multidrug-resistance from CAUTI-related pathogens. Importantly, CAUTI often leads to secondary bloodstream infections and death. A major challenge is to predict when patients will develop CAUTIs and which populations are at-risk for bloodstream infections. Catheter-induced inflammation promotes fibrinogen (Fg) and fibrin accumulation in the bladder which are exploited as a biofilm formation platform by CAUTI pathogens. Using our established mouse model of CAUTI, here we identified that host populations exhibiting either genetic or acquired fibrinolytic-deficiencies, inducing fibrin deposition in the catheterized bladder, are predisposed to severe CAUTI and septicemia by diverse uropathogens in mono- and poly-microbial infections. Furthermore, here we found that Enterococcus faecalis, a prevalent CAUTI pathogen, uses the secreted protease, SprE, to induce fibrin accumulation and create a niche ideal for growth, biofilm formation, and persistence during CAUTI.
Funding Information
  • U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (R01DK128805, R01DK051406)
  • U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (R21AI163825, U19AI157797)
  • U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases
  • U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (R01-HL013423, U01-HL143403)
  • U.S. Department of Health & Human Services | NIH | Center for Information Technology (R01-HL160046)
  • U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute
  • U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases
  • -Good Venture Foundation/Open Philanthropy Foundation -College of Science’s Paul F. Ware, M.D. Graduate Fellowship

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