A murine model for catheter-associated candiduria

Wang, Xiabo; Fries, Bettina C.

doi:10.1099/jmm.0.026294-0

Cited by 40 publications

(39 citation statements)

References 47 publications

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“…3). This is in contrast to what has been observed in a prior CAUTI model of C. albicans infection and in a rat venous catheter biofilm infection, both of which had used polyethylene catheters (17,55). We suspect that the dehydration process required for SEM altered the silicone, weakening the biofilm binding.…”

Section: Figcontrasting

confidence: 54%

“…One limitation of the previously described rodent CAUTI models is the placement of the catheter segments (53)(54)(55). Al-…”

Section: Discussionmentioning

confidence: 99%

“…Following transurethral inoculation, bacterial biofilms were established on the catheter surfaces and animals developed the histopathologic findings of acute pyelonephritis. This model was subsequently adapted for use in a mouse for study of Pseudomonas aeruginosa, Proteus mirabilis, Enterococcus faecalis, and Candida albicans (53)(54)(55). In an investigation of C. albicans biofilms by Wang and Fries, the catheter segments were secured in the bladder for 5 to 7 days prior to infection, allowing for host proteins to adsorb to the device surface (55).…”

Section: Discussionmentioning

confidence: 99%

“…This model was subsequently adapted for use in a mouse for study of Pseudomonas aeruginosa, Proteus mirabilis, Enterococcus faecalis, and Candida albicans (53)(54)(55). In an investigation of C. albicans biofilms by Wang and Fries, the catheter segments were secured in the bladder for 5 to 7 days prior to infection, allowing for host proteins to adsorb to the device surface (55). In this model, dense biofilms formed on both the luminal and external catheter surfaces and consisted of yeast and hyphae.…”

Section: Discussionmentioning

confidence: 99%

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Rat Indwelling Urinary Catheter Model of Candida albicans Biofilm Infection

et al. 2014

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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.

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Section: Figcontrasting

confidence: 54%

“…One limitation of the previously described rodent CAUTI models is the placement of the catheter segments (53)(54)(55). Al-…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Rat Indwelling Urinary Catheter Model of Candida albicans Biofilm Infection

et al. 2014

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“…However, these systems do not involve the continuous blood flow and the immune system of the host. This resulted in the development of in vivo model systems, such as the central venous catheter (CVC) model [8][9][10] , the denture stomatitis model of oral candidiasis 11 and a murine model for catheter-associated candiduria 12 . Additionally, C. albicans biofilm development was studied in vivo on the mucosal surfaces, such as those from the vagina 13 and oral cavity 14 .…”

Section: Introductionmentioning

confidence: 99%

<em>Candida albicans</em> Biofilm Development on Medically-relevant Foreign Bodies in a Mouse Subcutaneous Model Followed by Bioluminescence Imaging

Kucharíková

Velde

Himmelreich

et al. 2015

JoVE

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Candida albicans biofilm development on biotic and/or abiotic surfaces represents a specific threat for hospitalized patients. So far, C. albicans biofilms have been studied predominantly in vitro but there is a crucial need for better understanding of this dynamic process under in vivo conditions. We developed an in vivo subcutaneous rat model to study C. albicans biofilm formation. In our model, multiple (up to 9) Candidainfected devices are implanted to the back part of the animal. This gives us a major advantage over the central venous catheter model system as it allows us to study several independent biofilms in one animal. Recently, we adapted this model to study C. albicans biofilm development in BALB/c mice. In this model, mature C. albicans biofilms develop within 48 hr and demonstrate the typical three-dimensional biofilm architecture. The quantification of fungal biofilm is traditionally analyzed post mortem and requires host sacrifice. Because this requires the use of many animals to perform kinetic studies, we applied non-invasive bioluminescence imaging (BLI) to longitudinally follow up in vivo mature C. albicans biofilms developing in our subcutaneous model. C. albicans cells were engineered to express the Gaussia princeps luciferase gene (gLuc) attached to the cell wall. The bioluminescence signal is produced by the luciferase that converts the added substrate coelenterazine into light that can be measured. The BLI signal resembled cell counts obtained from explanted catheters. Non-invasive imaging for quantifying in vivo biofilm formation provides immediate applications for the screening and validation of antifungal drugs under in vivo conditions, as well as for studies based on host-pathogen interactions, hereby contributing to a better understanding of the pathogenesis of catheter-associated infections. Video LinkThe video component of this article can be found at

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Galleria mellonella as an alternative in vivo model to study implant‐associated fungal infections

Mannala

Rupp

Walter

et al. 2023

Journal Orthopaedic Research

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Fungal implant‐associated bone infections are rare but difficult to treat and often associated with a poor outcome for patients. Candida species account for approximately 90% of all fungal infections. In vivo biofilm models play a major role to study biofilm development and potential new treatment options; however, there are only a very few in vivo models to study fungi‐associated biofilms. Furthermore, mammalian infection models are replaced more and more due to ethical restrictions with other alternative models in basic research. Recently, we developed an insect infection model with Galleria mellonella larvae to study biofilm‐associated infections with bacteria. Here, we further expanded the G. mellonella model to study in vivo fungal infections using Candida albicans and Candida krusei. We established a planktonic and biofilm‐implant model to test different antifungal medication with amphotericin B, fluconazole, and voriconazole against the two species and assessed the fungal biofilm‐load on the implant surface. Planktonic infection with C. albicans and C. krusei showed the killing of the G. mellonella larvae at 5 × 105 colony forming units (CFU). Treatment of larvae with antifungal compounds with amphotericin B and fluconazole showed significant survival improvement against planktonic C. albicans infection, but voriconazole had no effect. Titanium and stainless steel K‐wires were preincubated with C. albicans and implanted inside the larvae to induce biofilm infection on the implant surface. The survival analysis revealed significantly reduced survival of the larvae with Candida spp. infection compared to noninfected implants. The treatment with antifungal amphotericin B and fluconazole resulted in a slight and nonsignificant improvement survival of the larvae. The treatment with the antifungal compounds in the biofilm‐infection model was not as effective as in the planktonic infection model, which highlights the resistance of fungal biofilms to antifungal compounds like in bacterial biofilms. Scanning electron microscopy (SEM) analysis revealed the formation of a fungal biofilm with hyphae and spores associated with larvae tissue on the implant surface. Thus, our study highlights the use of G. mellonella larvae as alternative in vivo model to study biofilm‐associated implant fungal infections and that fungal biofilms exhibit high resistance profiles comparable to bacterial biofilms. The model can be used in the future to test antifungal treatment options for fungal biofilm infections.

show abstract

A murine model for catheter-associated candiduria

Cited by 40 publications

References 47 publications

Rat Indwelling Urinary Catheter Model of Candida albicans Biofilm Infection

Rat Indwelling Urinary Catheter Model of Candida albicans Biofilm Infection

<em>Candida albicans</em> Biofilm Development on Medically-relevant Foreign Bodies in a Mouse Subcutaneous Model Followed by Bioluminescence Imaging

Galleria mellonella as an alternative in vivo model to study implant‐associated fungal infections

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