TY - JOUR
T1 - Fibrinolytic-deficiencies predispose hosts to septicemia from a catheter-associated UTI
AU - Molina, Jonathan J.
AU - Kohler, Kurt N.
AU - Gager, Christopher
AU - Andersen, Marissa J.
AU - Wongso, Ellsa
AU - Lucas, Elizabeth R.
AU - Paik, Andrew
AU - Xu, Wei
AU - Donahue, Deborah L.
AU - Bergeron, Karla
AU - Klim, Aleksandra
AU - Caparon, Michael G.
AU - Hultgren, Scott J.
AU - Desai, Alana
AU - Ploplis, Victoria A.
AU - Flick, Matthew J.
AU - Castellino, Francis J.
AU - Flores-Mireles, Ana L.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85188933301&partnerID=8YFLogxK
U2 - 10.1038/s41467-024-46974-6
DO - 10.1038/s41467-024-46974-6
M3 - Article
C2 - 38538626
AN - SCOPUS:85188933301
SN - 2041-1723
VL - 15
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2704
ER -