Inhibiting host-protein deposition on urinary catheters reduces associated urinary tract infections

eLife

Alyssa Ann La Bella¹  Jonathan Jesus Molina²  Marissa Jeme Andersen²  Alex Molesan²  Matthew M Champion²  Ana L Flores-Mireles³  ChunKi Fong³  Caitlin Howell⁴ 

[1] Graduate School of Biomedical Science and Engineering, University of Maine, Orono, United States;Department of Biological Sciences, College of Science, University of Notre Dame, Notre Dame, United States;Department of Chemical and Biomedical Engineering, College of Engineering, University of Maine, Orono, United States;Department of Chemistry and Biochemistry, College of Science, University of Notre Dame, Notre Dame, United States;

关键词: fibrinogen;    CAUTI;    slippery liquid-infused porous surface;    urinary catheter;    inflammation;    uropathogen;   

DOI  :  10.7554/eLife.75798

来源: DOAJ

【 摘 要 】

Microbial adhesion to medical devices is common for hospital-acquired infections, particularly for urinary catheters. If not properly treated these infections cause complications and exacerbate antimicrobial resistance. Catheter use elicits bladder inflammation, releasing host serum proteins, including fibrinogen (Fg), into the bladder, which deposit on the urinary catheter. Enterococcus faecalis uses Fg as a scaffold to bind and persist in the bladder despite antibiotic treatments. Inhibition of Fg–pathogen interaction significantly reduces infection. Here, we show deposited Fg is advantageous for uropathogens E. faecalis, Escherichia coli, Pseudomonas aeruginosa, K. pneumoniae, A. baumannii, and C. albicans, suggesting that targeting catheter protein deposition may reduce colonization creating an effective intervention for catheter-associated urinary tract infections (CAUTIs). In a mouse model of CAUTI, host-protein deposition was reduced, using liquid-infused silicone catheters, resulting in decreased colonization on catheters, in bladders, and dissemination in vivo. Furthermore, proteomics revealed a significant decrease in deposition of host-secreted proteins on liquid-infused catheter surfaces. Our findings suggest targeting microbial-binding scaffolds may be an effective antibiotic-sparing intervention for use against CAUTIs and other medical device infections.

【 授权许可】

Unknown