Rat Indwelling Urinary Catheter Model of Candida albicans Biofilm Infection

Abstract

Indwelling urinary catheters are commonly used in the management of hospitalized patients. Candida can adhere to the device surface and propagate as a biofilm. These Candida biofilm communities differ from free-floating Candida, exhibiting high tolerance to antifungal therapy. The significance of catheter-associated candiduria is often unclear, and treatment may be problematic considering the biofilm drug-resistant phenotype. Here we describe a rodent model for the study of urinary catheter-associated Candida albicans biofilm infection that mimics this common process in patients. In the setting of a functioning, indwelling urinary catheter in a rat, Candida proliferated as a biofilm on the device surface. Characteristic biofilm architecture was observed, including adherent, filamentous cells embedded in an extracellular matrix. Similar to what occurs in human patients, animals with this infection developed candiduria and pyuria. Infection progressed to cystitis, and a biofilmlike covering was observed over the bladder surface. Furthermore, large numbers of C. albicans cells were dispersed into the urine from either the catheter or bladder wall biofilm over the infection period. We successfully utilized the model to test the efficacy of antifungals, analyze transcriptional patterns, and examine the phenotype of a genetic mutant. The model should be useful for future investigations involving the pathogenesis, diagnosis, therapy, prevention, and drug resistance of Candida biofilms in the urinary tract.

Plasticity of Candida albicans Biofilms

“…Using the XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxianilide] reduction assay, Uppuluri et al (204) demonstrated that biofilms formed in SU medium were as metabolically active as those grown in RPMI 1640 medium, although in SU medium, the final concentration of cells was lower, the hyphae were shorter, the biofilm architecture was less complex, and the expression of select filamentation-associated genes (EFG1, ALS3, and HWP1) was reduced. As is the case for the intravenous catheter model, the urinary catheter model developed by Andes and coworkers (188,203,205,206) is extremely effective for studying urinary catheter infections. In a subcutaneous model, van Dijck and coworkers (207,208) seeded pieces of catheter with implanted C. albicans yeast cells subcutaneously in the back of a mouse (Fig.…”

“…This model has also not been adopted generally, for the same reasons noted for the model of Andes et al (36), but it also appears to be an excellent one for studying catheter infections. A urinary catheter model, also developed by Andes and coworkers (203) and diagrammed in Fig. 5B, involved inserting a silicone catheter into the urethra of an immunosuppressed rat treated with antibiotics ( Fig.…”

Host Contributions to Construction of Three Device-Associated Candida albicans Biofilms

“…A rat urinary catheter biofilm model was used as a model to mirror indwelling urinary catheter infections in patients (14). Briefly, animals received a single dose of cortisone acetate (250 mg/kg) subcutaneously.…”

“…For examination of the extracellular matrix composition of in vivo Candida biofilms, we chose to include three rat models of C. albicans biofilm infection that closely mimic common clinical scenarios (14)(15)(16). Mature biofilms formed on the surfaces of these devices, including a vascular catheter, urinary catheter, and denture device, contained abundant extracellular matrix material as visualized by scanning electron microscopy (Fig.…”

“…This investigation explores the host contribution to Candida biofilms in clinically relevant animal models representing the most common Candida device infections (14)(15)(16)(17). Exposure to host cells and proteins is a dynamic process specific to the infectious niche.…”