A Periprosthetic Joint Candida albicans Infection Model in Mouse

Summary

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.

Abstract

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&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.

Introduction

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 patients^2,3. 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 tissues^4,5. Besides, C. albicans can form biofilms on the surfaces of biomedical ma....

Protocol

The animals were purchased from Xi'an Jiaotong University. All animal experiment procedures were approved by the Institutional Animal Ethical Committee of Xi'an Jiaotong University (approval number: SCXK [Shaanxi] 2021-103). The mice were kept for one week with 5 mice per cage. They were allowed free access to food and water. The animals were maintained at room temperature (RT; 24 °C ± 1 °C) and light/dark cycle (12 h/12 h) before the study was performed.

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Discussion

The infection caused by the contamination of surgical instruments or the surgical environment during surgery is the major reason for most implant infections^24,25,26,27. Therefore, a mouse C. albicans biofilm-related PJI model was constructed in this study. Compared to the traditional PJI model in which sterile stainless-steel particles suspended in saline were used as the implant, a ni.......

Materials

Name	Company	Catalog Number	Comments
0.5 Mactutrius turbidibris	Shanghai Lujing Technology Co., Ltd	5106063
4 °C refrigerator	Electrolux (China) Electric Co., Ltd	ESE6539TA
Agar	Beijing Aoboxing Bio-tech Co., Ltd	01-023
Analytical balances	Shimadzu	ATX124
Autoclaves Sterilizer	SANYO	MLS-3750
Carbenicillin	Amresco	C0885
Eclipse Ci Nikon upright optical microscope	Nikon	Eclipse Ts2-FL
Glucose	Macklin	D823520
Inoculation ring	Thermo Scientific	251586
Isoflurane	RWD	20210103
NaCl	Xi'an Jingxi Shuanghe Pharmaceutical Co., Ltd	20180108
Paraformaldehyde	Beyotime Biotechnology	P0099
Peptone	Beijing Aoboxing Bio-tech Co., Ltd	01-001
RWD R550 multi-channel small animal anesthesia machine	RWD	R550
SEM	Hitachi	TM-1000
Temperature incubator	Shanghai Zhichu Instrument Co., Ltd	ZQTY-50N
Ultrapure water water generator	Heal Force	NW20VF
Ultrasound machine	Do-Chrom	DS10260D
Yeast extract	Thermo Scientific Oxoid	LP0021B