Discovery of a polymer resistant to bacterial biofilm, swarming, and encrustation

Abstract

Innovative approaches to prevent catheter-associated urinary tract infections (CAUTIs) are urgently required. Here, we describe the discovery of an acrylate copolymer capable of resisting single- and multispecies bacterial biofilm formation, swarming, encrustation, and host protein deposition, which are major challenges associated with preventing CAUTIs. After screening ~400 acrylate polymers, poly( tert -butyl cyclohexyl acrylate) was selected for its biofilm- and encrustation-resistant properties. When combined with the swarming inhibitory poly(2-hydroxy-3-phenoxypropyl acrylate), the copolymer retained the bioinstructive properties of the respective homopolymers when challenged with Proteus mirabilis , Pseudomonas aeruginosa , Staphylococcus aureus , and Escherichia coli . Urinary tract catheterization causes the release of host proteins that are exploited by pathogens to colonize catheters. After preconditioning the copolymer with urine collected from patients before and after catheterization, reduced host fibrinogen deposition was observed, and resistance to diverse uropathogens was maintained. These data highlight the potential of the copolymer as a urinary catheter coating for preventing CAUTIs.

Smart Lubricant Coating with Urease‐Responsive Antibacterial Functions for Ureteral Stents to Inhibit Infectious Encrustation

“…As the most dominant strain causing bacterial infection strain isolated from US encrustation and blockages, Proteus mirabilis (P. mirabilis) has been found to secrete large amounts of urease during proliferation. [12] This is problematic because urease has a high selectivity to the urea linkage of urinary urea, which can catalyze the hydrolysis of urinary urea to ammonia and increase the urine pH, accelerating the precipitation of Ca 2+ and Mg 2+ crystals and ultimately resulting in encrustation and blockage of the flow channels of stents in a short time. [12,23] Here, we hypothesized that this enzyme activity could act as a biological signal to trigger the selective cleavage of urea linkages in the SA-PU/PVP coating.…”

“…[11] Despite this approach being efficient, an increasing number of studies have revealed that the prophylactic application of this strategy can also favor the development of antibacterial resistance because of the uncontrolled and imprecise release profile of incorporated antibiotics. [12] Therefore, "on-demand" release of antibiotics from the antifouling coating triggered by the stimuli (e.g., pH, temperature, and enzymes) in the microenvironment of biofilms is considered as a smart approach to achieve precise antibiotic delivery for reducing the incidence of UTIs and encrustation. [13] In clinical studies, Proteus mirabilis (P. mirabilis) was the most prevalent bacteria in US surface biofilms, which secretes a significant amount of urease that can further promote the deposition of urate crystals.…”

“…[13] In clinical studies, Proteus mirabilis (P. mirabilis) was the most prevalent bacteria in US surface biofilms, which secretes a significant amount of urease that can further promote the deposition of urate crystals. [12,14] Therefore, in the urinary tract microenvironment, urease can be utilized as a specific stimulus to trigger the "on-demand" release of antibiotics for use against UTIs and Proteus-driven encrustation. Herein, we propose the development of a synergistic antifouling and urease-responsive smart antibacterial surface coating to effectively inhibit UTIs and encrustation (as illustrated in Scheme 1).…”

Virtual High‐Throughput Screening of Vapor‐Deposited Amphiphilic Polymers for Inhibiting Biofilm Formation

“…[ 5,6 ] Successful examples of such materials include poly(ethylene glycol) brushes, [ 7 ] zwitterionic polymers, [ 8 ] liquid‐infused surfaces, [ 9 ] and amphiphilic copolymers (AP). [ 10–15 ] Here, we focus on AP for their capability in mitigating bacterial attachment and biofilm formation at both solid–liquid interfaces and solid–liquid–gas triple interfaces, the latter of which has received far less attention despite their implication in nosocomial material‐associated infections. [ 12 ]…”

“…[5,6] Successful examples of such materials include poly(ethylene glycol) brushes, [7] zwitterionic polymers, [8] liquid-infused surfaces, [9] and amphiphilic copolymers (AP). [10][11][12][13][14][15] Here, we focus on AP for their capability in mitigating bacterial attachment and biofilm formation at both solid-liquid interfaces and solid-liquid-gas triple interfaces, the latter of which has received far less attention despite their implication in nosocomial material-associated infections. [12] While the antibiofouling performance of most polymer coatings has been attributed to hydrophilicity, i.e., the increased enthalpic barrier for foulant adhesion, the fundamental mechanism for AP's fouling resistance is not well understood.…”