A Catheter-Related Candida albicans Infection Model in Mouse
March 22nd, 2024
We establish a mouse model of C.albicans-associated catheter-related infection (CRI), in which biofilm forms on the catheter, and the interaction between C.albicans and host correlates well with the clinical CRI. This model helps screen therapies for C.albicans biofilm-associated CRI, laying a foundation for clinical transformation.
Our research aims to establish a mouse model of Candida albicans associated catheter-related infection in which biofilm forms on the catheter. This model is helpful for correlating with the clinical CRI and the interaction between Candida albicans and host. The existing animal models of Candida albicans such as offering candidiasis model, general candida model, and invasive systemic infection model caused by candidiasis cannot correlate well with clinical CRI.
To improve Candida albicans detection in catheter infections, our protocol employed a strain with enhanced green fluorescein protein. This allowed for clear visualization of Candida albicans colony and biofilms in catheters in mice and in timely detection. To begin, group 30 mice into three groups labeled control, catheter, and model.
Place an anesthetized mouse in a prone position on the operating table, shave the back of the animal, then disinfect the surgical site with iodaphor. For the mice in the catheter group, insert a one milliliter sterile syringe needle into the surgical site to make a hole. Then remove the syringe needle and insert a one centimeter long catheter into the hole.
For the mice in the model group, pipette 200 microliters of Candida albican suspension onto the surgical site. After the suspension has been absorbed into the skin, insert a one milliliter sterile syringe needle into the site. Then insert the catheter into the hole created by the needle.
Pipette 20 microliters of the Candida albican suspension along the catheter to the tissue. Then fix the catheters with tape and gauze before returning them to the cages for feeding. After three days, collect the catheters and skin tissue samples from the back of the euthanized mice.
Fix the catheters in 4%paraformaldehyde at four degrees Celsius for 48 hours. Then use a fluorescent microscope to record the images of the yeast biofilm at 484 nanometers. Following this, analyze the images of the histopathologically stained skin tissues for changes.
No obvious fluorescence was observed on the surface of the polyethylene catheters in the catheter group. Strong fluorescence emitted by adherent Candida albicans cells was visible on the catheter surface in the model group. Shaft poriodate standing of the control and catheter skin tissues showed the absence of Candida albicans.
A small number of positive C.albicans cells were observed in the model group. The candida infection resulted in the thickening and extension of the epidermis layer with visible inflammation infiltration in the model group. Both the control and catheter groups had intact epidermis layer, dermis layer, sebaceous glands, hair follicles, and other structures.
Overview
This study establishes a mouse model of Candida albicans-associated catheter-related infection (CRI) that effectively mimics clinical conditions. The model facilitates the evaluation of therapies targeting C. albicans biofilm-associated CRI.
Key Study Components
Area of Science
- Microbiology
- Infectious Diseases
- Animal Models
Background
- Candida albicans is a common pathogen in catheter-related infections.
- Existing animal models do not adequately represent clinical CRI.
- Biofilm formation on catheters complicates treatment and detection.
- Enhanced visualization techniques are necessary for effective research.
Purpose of Study
- To develop a reliable mouse model for studying C. albicans CRI.
- To correlate findings with clinical CRI scenarios.
- To improve detection methods for C. albicans in catheter infections.
Methods Used
- Grouping of 30 mice into control, catheter, and model groups.
- Use of a strain with enhanced green fluorescein protein for visualization.
- Assessment of biofilm formation on catheters.
- Correlation of model results with clinical data.
Main Results
- Successful establishment of a mouse model for C. albicans CRI.
- Clear visualization of biofilms using enhanced fluorescent techniques.
- Demonstrated correlation between the model and clinical CRI.
- Provided a foundation for future therapeutic screening.
Conclusions
- The mouse model is a valuable tool for studying C. albicans CRI.
- Enhanced visualization aids in timely detection of infections.
- This model can facilitate the development of new therapies.
Frequently Asked Questions
Executive Industry Relevance
Establishing a robust mouse model for catheter-related Candida albicans infection addresses a critical gap in preclinical infectious disease research. This model enables predictive evaluation of antifungal strategies targeting biofilm-associated device infections, directly informing early-stage therapeutic screening and mechanistic de-risking. Its translational alignment with clinical CRI scenarios enhances portfolio confidence for anti-biofilm intervention programs.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Enables interrogation of C. albicans biofilm formation and host-pathogen interactions on medical devices.
- Supports biological de-risking by modeling clinically relevant infection mechanisms.
- Facilitates functional validation of antifungal targets in a disease-relevant system.
Screening & Assay Development
- Provides a standardized in vivo platform for quantitative assessment of biofilm inhibition.
- Enables reproducible visualization of fungal colonization using fluorescent markers.
- Supports assay readiness for preclinical compound evaluation against device-associated infections.
Translational & Preclinical Research
- Aligns with clinical pathology by recapitulating biofilm-driven CRI and associated tissue responses.
- Enables continuity from discovery through preclinical validation of anti-biofilm therapeutics.
- Supports risk-adjusted advancement decisions for anti-infective candidates targeting device-related infections.
Pipeline & Workflow Integration
This mouse model integrates into the discovery-to-preclinical continuum for anti-infective R&D, bridging early mechanistic studies and translational validation of candidate therapies.
- Discovery Biology: Supports hypothesis testing on biofilm formation and host response in a controlled in vivo context.
- Screening: Delivers quantitative, reproducible readouts of fungal colonization and biofilm development.
- Analytics: Enables comparative analysis of infection severity and therapeutic efficacy using fluorescence and histopathology.
- Translational Research: Provides a clinically relevant model for evaluating intervention strategies prior to human studies.
- Enterprise Reuse: Offers a reusable platform for iterative testing of anti-biofilm agents and device coatings.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence for anti-biofilm target validation and mechanistic de-risking.
- Operational Value: Standardizes in vivo infection modeling and quantitative assessment workflows.
- Strategic Value: Improves go/no-go decision-making for anti-infective portfolios targeting device-associated infections.
- Portfolio Impact: Enables risk-adjusted prioritization of candidates with translational relevance to clinical CRI.
Implementation Considerations
- Requires expertise in animal handling, surgical catheter placement, and infection modeling.
- Needs access to fluorescence imaging and histopathological analysis infrastructure.
- Demands cross-team standardization of infection protocols and readout criteria.
- Adaptation may be needed for different catheter materials or fungal strains.
- Model limitations include species-specific host responses and scalability for high-throughput screening.
