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.
Nature communications. 2024 Mar 27*** epublish ***
Jonathan J Molina, Kurt N Kohler, Christopher Gager, Marissa J Andersen, Ellsa Wongso, Elizabeth R Lucas, Andrew Paik, Wei Xu, Deborah L Donahue, Karla Bergeron, Aleksandra Klim, Michael G Caparon, Scott J Hultgren, Alana Desai, Victoria A Ploplis, Matthew J Flick, Francis J Castellino, Ana L Flores-Mireles
Integrated Biomedical Sciences, University of Notre Dame, Notre Dame, IN, 46556, USA., Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, 46556, USA., Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA., W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN, 46556, USA., Department of Surgery, Washington University School of Medicine, St. Louis, MO, 63110, USA., Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA., Integrated Biomedical Sciences, University of Notre Dame, Notre Dame, IN, 46556, USA. .