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Unveiling Host-Pathogen Interactions During Catheter-Associated Urinary Tract Infection to Develop a Novel Catheter Material to Reduce Infections: Creating an Efficient Intervention Strategy

thesis
posted on 2024-02-12, 19:34 authored by Marissa J. Andersen

Microbial adhesion to medical devices is common in hospital acquired infections, particularly, those associated with urinary catheters. If not properly treated these infections can lead to further patient complications and exacerbate antimicrobial use and resistance. Studies show the placement of urinary catheters leads to bladder inflammation by causing mechanical damage to the bladder epithelium (urothelium). To heal the damaged tissue, host serum proteins are released into the bladder and are consequently deposited on the urinary catheter. Importantly, it’s been shown that Enterococcus faecalis uses the serum protein fibrinogen (Fg) as a scaffold to bind and persist in the catheterized bladder despite antibiotic treatments while inhibition of this interaction significantly reduces catheter-associated urinary tract infection (CAUTI). These studies show that deposited Fg is advantageous for not only E. faecalis but also other uropathogens such as S. aureus, A. baumannii and the fungal species C. albicans. Building on these studies I show Fg is advantageous to other uropathogens including Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Additionally, I showed that a liquid-infused silicone catheter is able to decrease deposition of Fg and other host proteins on the catheter using proteomic analysis. Furthermore, this modification reduced microbial burden in the bladders and on catheters during acute and prolonged murine CAUTI. Moreover, CAUTIs often lead to systemic dissemination; importantly, this novel catheter reduces systemic dissemination for most uropathogens. I also showed this modification retains its anti-fouling ability at less than full silicone oil infusion. These findings show that targeting and removing microbial binding scaffolds is an effective and antibiotic-sparing prevention strategy for use against CAUTIs and should be expanded to other infections associated with medical devices. I have also shown that polymicrobial interactions between E. faecalis and P. mirabilis in the catheterized bladder change the 3D architecture of microbial biofilms. Lastly, fungal CAUTI specifically caused by Candida spp. have become more prevalent and I reveled that C. albicans hyphal formation results in a robust neutrophil infiltration into the bladder during infection.

History

Defense Date

2023-11-01

CIP Code

  • PHD-BIOS

Research Director(s)

Ana L. Flores-Mireles

Degree

  • Doctor of Philosophy

Degree Level

  • Doctoral Dissertation

OCLC Number

1411844546

Program Name

  • Biological Sciences (BIOS)

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