establishment and evaluation of a mouse catheter-related infection model

Establishing a Mouse Model for &lt;em&gt;Candida albicans&lt;/em&gt;-Associated Catheter-Related Infection

In recent years, with the development and application of biomedical materials, implant-related infections are emerging as difficult clinical problems1,2. With the wide application of medical catheters in clinics, the number of related infections and deaths is huge every year3,4. The common infection routes of a catheter-related infection (CRI) include: (1) pathogens on the surface of the skin infiltrate into the body and adhere to the outer surface of the catheter5,6,7; (2) improper aseptic operation-derived pathogens invade, adhere and colonize on the catheter; (3) pathogens in the blood circulation adhere and colonize on the catheter; (4) drugs contaminated by pathogenic microorganism.
Candida is the third most common reason for CRI8,9. It is very likely to cause bloodstream infection and other life-threatening invasive candidiasis after biofilms are formed on the surface of the implant. The prognosis is poor, and the mortality rate is high2. It is reported that biofilms are formed on the surface of the catheter within 2 weeks after central venous insertion and in the lumen of the catheter a few weeks later10,11.
Candida albicans (C. albicans) biofilms formed on medical catheters exhibit a double-layer network composed of yeast, stroma, and mycelium12,13. The formation of C. albicans biofilms is not only a key for drug resistance and immune evasion13 but also vital to produce disseminated spores, which leads to further hematogenous infection2,12 and results in more serious and even life-threatening consequences. C. albicans-associated CRI is a major cause of clinical fungal bloodstream infections7,14, and more than 40% of patients with C. albicans infection in the central venous catheter will develop into bacteremia15.
According to the Infectious Disease Society of America, the recommended treatment of Candida CRI includes (1) removal of the infected catheter; (2) subjecting the patients to a 14 days-systemic antifungal therapy8; (3) reimplanting a new catheter4. However, in clinical applications, catheters cannot be fully removed sometimes. Some patients can only be treated with systemic antibiotics and antimicrobial lock therapy, accompanied by strong side effects16,17.
Existing animal models of C. albicans, such as the oropharyngeal candidiasis model, vaginal candidiasis model, and invasive systemic infection model caused by candidiasis18,19 cannot correlate well with the clinical CRI. Therefore, in this study, a C. albicans-associated CRI model in mice was established. Clinical commonly used polyethylene catheters were used as subcutaneous implants20,21, and C. albicans were inoculated on the skin surface to simulate the adhesion of C. albicans to the medical catheters and the formation of biofilms.
This model has been successfully used in our laboratory to screen the anti-biofilm effect of different therapeutics22. In addition, due to the lag detection of C. albicans after catheter infection, a C. albicans strain containing enhanced green fluorescent protein (EGFP) was constructed and inoculated in mice to facilitate the intuitive observation of the colonies and biofilms of C. albicans on the implanted catheter.

Author Spotlight: Enhancing Candida albicans Detection in Catheter Infections Using Fluorescent Protein Tagging 

A Catheter-Related Candida albicans Infection Model in Mouse

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 the oropharyngeal candidiasis model, vaginal candidiasis model, and invasive systemic infection model caused by candidiasis cannot correlate well with the clinical CRI.To improve Candida albicans detection in catheter infections, our protocol employed a stain with enhanced green fluorescein protein. This allowed for clear visualization of Candida albicans colony and biofilms on catheters in mice, and in timely detection.

Watch this Scientific Journal Video about Establishment and Evaluation of a Mouse Catheter-Related Infection Model at JoVE.com

Establishment and Evaluation of a Mouse Catheter-Related Infection Model  

establishment-evaluation-mouse-catheter-related-infection

Research

JoVE Journal

Immunology and Infection

319 vues.  Xi’an Jiaotong University. Pour commencer, regroupez 30 souris en trois groupes étiquetés contrôle, cathéter et modèle. Placez une souris anesthésiée en position couchée sur la table d’opération. Rasez le dos de l’animal, puis désinfectez le site chirurgical avec de l’iodophore.Pour les souris du groupe cathéter, insérez une aiguille de seringue stérile d’un millilitre dans le site chirurgical pour faire un trou. Retirez ensuite l’aiguille de la seringue et insérez un cathéter d’un cen...

Vidéo: Establishment and Evaluation of a Mouse Catheter-Related Infection Model  

Catheter-related infection (CRI) is a common nosocomial infection caused by candida albicans during catheter implantation. Typically, biofilms are formed on the outer surface of the catheter and lead to disseminated infections, which are fatal to patients. There are no effective prevention and treatment management in clinics. Therefore, it is urgent to establish an animal model of CRI for the preclinical screening of new strategies for its prevention and treatment. In this study, a polyethylene catheter, a widely used medical catheter, was inserted into the back of the BALB/c mice after hair removal. Candida albicans ATCC MYA-2876 (SC5314) expressing enhanced green fluorescent protein was subsequently inoculated on the skin's surface along the catheter. Intense fluorescence was observed on the surface of the catheter under a fluorescent microscope 3 days later. Mature and thick biofilms were found on the surface of the catheter via scanning electron microscopy. These results indicated the adhesion, colonization, and biofilm formation of candida albicans on the surface of the catheter. The hyperplasia of the epidermis and the infiltration of inflammatory cells in the skin specimens indicated the histopathological changes of the CRI-associated skin. To sum up, a mouse CRI model was successfully established. This model is expected to be helpful in the research and development of therapeutic management for candida albicans associated CRI.

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.

Catheter-related infection (CRI) is a common nosocomial infection caused by candida albicans during catheter implantation. Typically, biofilms are formed ...