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

Abstract

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, into the bladder, which deposit on the urinary catheter. Enterococcus faecalis uses fibrinogen as a scaffold to bind and persist in the bladder despite antibiotic treatments. Inhibition of fibrinogen-pathogen interaction significantly reduces infection. Here, we show deposited fibrinogen is advantageous for uropathogens E. faecalis, E. coli, P. 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. 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 catheter-associated urinary tract infections and other medical device infections.

Data availability

The data that support the findings of this study are available in the source data. RAW and processed MS-MS/MS data are available in the MassIVE public repository, accession MSV000088527. This study did not generate new unique reagents.

The following data sets were generated

Article and author information

Author details

  1. Marissa Jeme Andersen

    Department of Biological Sciences, University of Notre Dame, Notre Dame, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. ChunKi Fong

    Department of Chemical and Biochemical Engineering, University of Maine, Orono, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Alyssa Ann La Bella

    Department of Biological Sciences, University of Notre Dame, Notre Dame, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jonathan Jesus Molina

    Department of Biological Sciences, University of Notre Dame, Notre Dame, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Alex J Molesan

    Department of Biological Sciences, University of Notre Dame, Notre Dame, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Matthew M Champion

    Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Caitlin Howell

    Department of Chemical and Biochemical Engineering, University of Maine, Orono, United States
    For correspondence
    caitlin.howell@maine.edu
    Competing interests
    The authors declare that no competing interests exist.
  8. Ana Lidia Flores-Mireles

    Department of Biological Sciences, University of Notre Dame, Notre Dame, United States
    For correspondence
    afloresm@nd.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4610-4246

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK128805)

  • Marissa Jeme Andersen
  • ChunKi Fong
  • Alex J Molesan
  • Caitlin Howell
  • Ana Lidia Flores-Mireles

Division of Chemical, Bioengineering, Environmental, and Transport Systems (CBET-2029378)

  • ChunKi Fong
  • Caitlin Howell

University of Notre Dame (FY19SEED6)

  • Marissa Jeme Andersen
  • Ana Lidia Flores-Mireles Dr.

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Marc J Bonten, University Medical Center Utrecht, Netherlands

Ethics

Animal experimentation: The University of Notre Dame Institutional Animal Care and Use Committee approved all mouse infections and procedures as part of protocol number 18-08-4792MD. All animal care was consistent with the Guide for the Care and Use of Laboratory Animals from the National Research Council. All catheterization and infection was done under Isoflurane anesthesia, sacrifices were done by Isoflurane overdose followed by cervical dislocation and every effort was made to minimize suffering

Human subjects: All participants signed an informed consent form and protocols were approved by the local Internal Review Board at the University of Notre Dame under study #19-04-5273.

Version history

  1. Received: November 23, 2021
  2. Preprint posted: December 7, 2021 (view preprint)
  3. Accepted: March 17, 2022
  4. Accepted Manuscript published: March 29, 2022 (version 1)
  5. Version of Record published: April 6, 2022 (version 2)

Copyright

© 2022, Andersen et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Marissa Jeme Andersen
  2. ChunKi Fong
  3. Alyssa Ann La Bella
  4. Jonathan Jesus Molina
  5. Alex J Molesan
  6. Matthew M Champion
  7. Caitlin Howell
  8. Ana Lidia Flores-Mireles
(2022)
Inhibiting host protein deposition on urinary catheters reduces associated urinary tract infections
eLife 11:e75798.
https://doi.org/10.7554/eLife.75798

Share this article

https://doi.org/10.7554/eLife.75798

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