evaluation of infection in major organs in the periprosthetic joint infection (pji) mouse model

Candida albicansバイオフィルム関連PJIのマウスモデルの確立

Candida albicans (C. albicans) commensally reside in many parts of the human body1, which is also the most common opportunistic pathogen that causes life-threatening invasive fungal infections, especially in immunocompromised patients2,3. C. albicans can transform between yeast and mycelium states as a polymorphic fungus. The mycelium state exhibits higher virulence, stronger adhesion, and invasion of cells and tissues4,5. Besides, C. albicans can form biofilms on the surfaces of biomedical materials such as dentures, catheters, and stents1,6,7. The dense three-dimensional structure of biofilms restricts the infiltration of antifungal drugs, expresses drug-resistant genes, and down-regulates the metabolism of fungal cells to resist immune system clearance6,7. Therefore, biofilms-related infections&#160;are quite challenging in clinics8.
Staphylococcus aureus, coagulase-negative staphylococcus, and enterobacter are the main pathogens causing PJI9. Although the incidence of fungal PJI is relatively low (about 1%)10, the treatment cost of fungal PJI is higher11, the treatment cycle is longer11, and the treatment success rate is lower10 than bacterial PJI. In recent years, the incidence of fungal PJI has been increasing year-by-year10. Candida PJI accounts for 77%-84% of fungal PJI10,12, and C. albicans is the most common in Candida (54%). Therefore, fungal PJI needs to be studied.
Currently, PJI is treated via revision surgery by (1) removing the infected implant, (2) debridement, (3) antimicrobial treatment, and (4) reimplantation. After thorough debridement, an antibiotic containing bone cement is placed, and the patient is treated with antibiotics systemically for more than 6 weeks to effectively control the infection before a new implant is placed13. However, this method cannot fully eliminate pathogens in tissues, and recurrent infections treated with long-term antimicrobial therapy are highly likely to develop in drug-resistant strains14,15,16.
Establishing animal models of PJI is important for the research and development of new drugs or therapeutics for PJI. In the development of PJI, large dead spaces are formed around the prosthesis, leading to the formation of hematomas, which further block the blood supply of the surrounding tissues and impair the effect of antibiotics11,15. Due to the difficulty in mimicking the surrounding environment of the prosthesis, traditional animal models cannot accurately simulate the actual situation of PJI17,18.
In this paper, a C. albicans biofilm-associated PJI model in mice was constructed by using a clinically widely used titanium-nickel wire to simulate joint implants19,20. This PJI model exhibits the advantages of easy operation, high successful rate, high repeatability, and high clinical correlation. It is expected to be an important model for studying the prevention and treatment of C. albicans biofilm-related PJI.

著者スポットライト:カンジダ・アルビカンスのバイオフィルム関連補綴関節感染症に関する研究の進展 

マウスにおける人工関節周囲カン ジダ・アルビカンス 感染モデル

Watch this Scientific Journal Video about Evaluation of Infection in Major Organs in the Periprosthetic Joint Infection PJI Mouse Model at JoVE.com

Evaluation of Infection in Major Organs in the Periprosthetic Joint Infection (PJI) Mouse Model  

人工関節周囲感染症(PJI)マウスモデルにおける主要臓器の感染評価

まず、カンジダ・アルビカンス・バイオフィルム関連PJIマウスモデルを作成します。モデル確立から14日後、マウスを安楽死させ、腎臓、肝臓、脾臓を採取します。臓器ごとに、500マイクロリットルの滅菌生理食塩水を導入します。ホモジナイザーで組織を摂氏4度で粉砕します。次に、調製したホモジネートを100マイクロリットルYPDプレートに加え、曲がったロッドを使用して均等に広げます。YPDプレートを逆さにして摂氏37度のインキュベーターに48時間置きます。インキュベーションの最後に、プレートを目視で調べ、目に見えるコロニーを数えます。

evaluation-infection-major-organs-periprosthetic-joint-infection-pji

Research

JoVE Journal

Immunology and Infection

Evaluation of Infection in Major Organs in the Periprosthetic Joint Infection (PJI) Mouse Model

65 ビュー. まず、カンジダ・アルビカンス・バイオフィルム関連PJIマウスモデルを作成します。モデル確立から14日後、マウスを安楽死させ、腎臓、肝臓、脾臓を採取します。臓器ごとに、500マイクロリットルの滅菌生理食塩水を導入します。ホモジナイザーで組織を摂氏4度で粉砕します。次に、調製したホモジネートを100マイクロリットルYPDプレートに加え、曲がったロッ?...

ビデオ: Evaluation of Infection in Major Organs in the Periprosthetic Joint Infection (PJI) Mouse Model  

A Periprosthetic Joint Candida albicans Infection Model in Mouse

Periprosthetic joint infection (PJI) is one of the common infections caused by Candida albicans (C. albicans), which increasingly concerns surgeons and scientists. Generally, biofilms that can shield C. albicans from antibiotics and immune clearance are formed at the infection site. Surgery involving the removal of the infected implant, debridement, antimicrobial treatment, and reimplantation is the gold standard for the treatment of PJI. Thus, establishing animal PJI models is of great significance for the research and development of new drugs or therapeutics for PJI. In this study, a smooth nickel-titanium alloy wire, a widely used implant in orthopedic clinics, was inserted into the femoral joint of a C57BL/6 mouse before the C. albicans were inoculated into the articular cavity along the wire. After 14 days, mature and thick biofilms were observed on the surface of implants under a scanning electronic microscope (SEM). A significantly reduced bone trabecula was found in the H&amp;E staining of the infected joint specimens. To sum up, a mouse PJI model with the advantages of easy operation, high successful rate, high repeatability, and high clinical correlation was established. This is expected to be an important model for clinical studies of C. albicans biofilm-related PJI prevention.

Periprosthetic joint infection (PJI) caused by dangerous pathogens is common in clinical orthopedics. Existing animal models cannot accurately simulate the actual situation of PJI. Here, we established a Candida albicans biofilm-associated PJI mouse model to research and develop new therapeutics for PJI.

Periprosthetic joint infection (PJI) is one of the common infections caused by Candida albicans (C. albicans), which increasingly concerns surgeons and ...