On-demand release of Candida albicans biofilms from urinary catheters by mechanical surface deformation

Abstract

Candida albicans is a leading cause of catheter-associated urinary tract infections and elimination of these biofilm-based infections without antifungal agents would constitute a significant medical advance. A novel urinary catheter prototype that utilizes on-demand surface deformation is effective at eliminating bacterial biofilms and here the broader applicability of this prototype to remove fungal biofilms has been demonstrated. C. albicans biofilms were debonded from prototypes by selectively inflating four additional intralumens surrounding the main lumen of the catheters to provide the necessary surface strain to remove the adhered biofilm. Deformable catheters eliminated significantly more biofilm than the controls (>90% eliminated vs 10% control; p < 0.001). Mechanical testing revealed that fungal biofilms have an elastic modulus of 45 ± 6.7 kPa with a fracture energy of 0.4-2 J m^-2. This study underscores the potential of mechanical disruption as a materials design strategy to combat fungal device-associated infections.

Keywords: Biofilm; Candida albicans; catheter-associated infection; elastic modulus; mechanical deformation; urinary catheter.

Figure 1.

Schematic of the experimental apparatus. A continuous supply of artificial urine medium (AUM) is provided to an artificial bladder using a peristaltic pump (flow rate = 0.5 mm min⁻¹). The top portion of the catheter is inserted into an artificial bladder while the bottom portion is connected to tubing that drains into a waste container. The entire apparatus is enclosed in a modified incubator at 37°C. Arrows symbolize the direction of medium flow. <<Editor: “artificial” should read “Artificial”, “catheter” = “Catheter”, “peristaltic = “Peristaltic” and “media” = “medium”>>

Figure 2.

Representative optical images of C. albicans biofilms grown in catheter prototypes compared to a negative control (A). Cross sectional optical images of biofilm growth within the main lumen at different regions along the length of the catheter prototype (B). Scale bars = 1 cm (upper) and 1 mm (lower).

Figure 3.

SEM images of C. albicans biofilms formed inside catheters. (A) 63X magnification with 30 kV and scale bar = 1 mm. (B) 1,000X mag, 5kV, scale bar = 50 μm. (C) 4,000X magnification, 5 kV, scale bar = 10 μm. (D) 10,000x magnification, 5 kV, scale bar = 5 μm.

Figure 4.

Tensile testing of intact C. ablicans biofilms formed in catheter prototypes. (A) Biofilms were manually extracted from catheter prototypes and mounted in a microstrain analyzer for tensile testing. (B) Representative stress-strain plot resulting from tensile testing of intact biofilms. <<Editor: “Experiment Data” should read “Experimental data” and “;Linear Fitting” should read “;Linear fitting”>>

Figure 5.

Catheter prototypes debond C. albicans biofilms. Representative cross sectional (A) and longitudinal (B) optical images of control (not inflated, left) and debonded (inflated, right) biofilms in the main lumen of the catheter prototypes. Biofilms were stained with crystal violet to enhance visualization. Scale bars = 2 mm (A) and 5 mm (B). (C) Percentage biofilm mass removed from the control and inflated catheters (N = 4). “***” indicates p < 0.001. <<Editor: ‘‘Percent Debonded’’ should read ‘‘Percentage debonded’’>>