title: Antifungal activity of a β-peptide in synthetic urine media: Toward materials-based approaches to reducing catheter-associated urinary tract fungal infections.
abstract: Catheter-associated urinary tract infections (CAUTI) are the most common type of hospital-acquired infection, with more than 30 million catheters placed annually in the US and a 10-30% incidence of infection. Candida albicans forms fungal biofilms on the surfaces of urinary catheters and is the leading cause of fungal urinary tract infections. As a step toward new strategies that could prevent or reduce the occurrence of C. albicans-based CAUTI, we investigated the ability of antifungal β-peptide-based mimetics of antimicrobial peptides (AMPs) to kill C. albicans and prevent biofilm formation in synthetic urine. Many α-peptide-based AMPs exhibit antifungal activities, but are unstable in high ionic strength media and are easily degraded by proteases-features that limit their use in urinary catheter applications. Here, we demonstrate that β-peptides designed to mimic the amphiphilic helical structures of AMPs retain 100% of their structural stability and exhibit antifungal and anti-biofilm activity against C. albicans in a synthetic medium that mimics the composition of urine. We demonstrate further that these agents can be loaded into and released from polymer-based multilayer coatings applied to polyurethane, polyethylene, and silicone tubing commonly used as urinary catheters. Our results reveal catheters coated with β-peptide-loaded multilayers to kill planktonic fungal cells for up to 21days of intermittent challenges with C. albicans and prevent biofilm formation on catheter walls for at least 48h. These new materials and approaches could lead to advances that reduce the occurrence of fungal CAUTI.
  
  
  
  Catheter-associated urinary tract infections are the most common type of hospital-acquired infection. The human pathogen Candida albicans is the leading cause of fungal urinary tract infections, and forms difficult to remove 'biofilms' on the surfaces of urinary catheters. We investigated synthetic β-peptide mimics of natural antimicrobial peptides as an approach to kill C. albicans and prevent biofilm formation in media that mimics the composition of urine. Our results reveal these mimics to retain structural stability and activity against C. albicans in synthetic urine. We also report polymer-based approaches to the local release of these agents within urinary catheter tubes. With further development, these materials-based approaches could lead to advances that reduce the occurrence of fungal urinary tract infections.
authors.affiliation: Department of Chemical and Biological Engineering, 1415 Engineering Drive, University of Wisconsin - Madison, Madison, WI 53706, USA.
authors.forename: Namrata
authors.initials: N
authors.lastname: Raman
authors.affiliation: Department of Chemical and Biological Engineering, 1415 Engineering Drive, University of Wisconsin - Madison, Madison, WI 53706, USA.
authors.forename: Myung-Ryul
authors.initials: MR
authors.lastname: Lee
authors.affiliation: Materials Science Program, 1509 University Avenue, University of Wisconsin - Madison, Madison, WI 53706, USA.
authors.forename: Angélica de L
authors.initials: AL
authors.lastname: Rodríguez López
authors.affiliation: Department of Chemical and Biological Engineering, 1415 Engineering Drive, University of Wisconsin - Madison, Madison, WI 53706, USA. Electronic address: sppalecek@wisc.edu.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Palecek
authors.affiliation: Department of Chemical and Biological Engineering, 1415 Engineering Drive, University of Wisconsin - Madison, Madison, WI 53706, USA; Department of Chemistry, 1101 University Avenue, University of Wisconsin - Madison, Madison, WI 53706, USA. Electronic address: dlynn@engr.wisc.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Lynn
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001672:Biocompatible Materials / Q000737:chemistry*; D018441:Biofilms / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D002942:Circular Dichroism; D065546:Drug Liberation; D008826:Microbial Sensitivity Tests; D008856:Microscopy, Fluorescence; D009181:Mycoses / Q000188:drug therapy* / Q000382:microbiology; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D020959:Polyethylene / Q000737:chemistry; D062885:Urinary Catheters / Q000382:microbiology*; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000382:microbiology*; D014556:Urine / Q000382:microbiology*
chemical_list: D000935:Antifungal Agents; D001672:Biocompatible Materials; D010455:Peptides; D020959:Polyethylene
keywords: Antifungal; Biofilms; Coatings; Multilayers; Urinary catheters; β-Peptides