We are grateful for the financial support from the Natural Science Foundation of Shaanxi Province (grant number 2021SF-118) and the National Natural Science Foundation of China (grant numbers 81973409, 82204631).

The animals were purchased from Xi&#39;an Jiaotong University. All animal experiment procedures were approved by the Institutional Animal Ethical Committee of Xi&#39;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 &#176;C &#177; 1 &#176;C) and light/dark cycle (12 h/12 h) before the study was performed.
1. Buffer...

Establishing a Mouse Model for &lt;em&gt;Candida albicans&lt;/em&gt; Biofilm-Related PJI

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L., Wilson, D., Hube, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Candida+albicans+pathogenicity+mechanisms.">Candida albicans pathogenicity mechanisms.</a> Virulence. 4 (2), 119-128 (2013).</li><li>Fan, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Candida+albicans+biofilms:+antifungal+resistance,+immune+evasion,+and+emerging+therapeutic+strategies.">Candida albicans biofilms: antifungal resistance, immune evasion, and emerging therapeutic strategies.</a> International Journal of Antimicrobial Agents. 60 (5-6), 106673 (2022).</li><li>Tong, Y., Tang, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Candida+albicans+infection+and+intestinal+immunity.">Candida albicans infection and intestinal immunity.</a> Microbiological Research. 198, 27-35 (2017).</li><li>Kanaguchi, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+salivary+protein+flow+and+indigenous+microorganisms+on+initial+colonization+of+Candida+albicans+in+an+in+vivo+model.">Effects of salivary protein flow and indigenous microorganisms on initial colonization of Candida albicans in an in vivo model.</a> Bmc Oral Health. 12, 36 (2012).</li><li>Gulati, M., Nobile, C. 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D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Model+development+for+determining+the+efficacy+of+a+combination+coating+for+the+prevention+of+perioperative+device+related+infections:+A+pilot+study.">Model development for determining the efficacy of a combination coating for the prevention of perioperative device related infections: A pilot study.</a> Journal of Biomedical Materials Research - Part B Applied Biomaterials. 101 (7), 1143-1153 (2013).</li><li>Mo, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vitro+and+in+vivo+effects+of+the+combination+of+myricetin+and+miconazole+nitrate+incorporated+to+thermosensitive+hydrogels,+on+C.+albicans+biofilms.">In vitro and in vivo effects of the combination of myricetin and miconazole nitrate incorporated to thermosensitive hydrogels, on C. albicans biofilms.</a> Phytomedicine. 71, 153223 (2020).</li><li>Zahar, A., Sarungi, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnosis+and+management+of+the+infected+total+knee+replacement:+a+practical+surgical+guide.">Diagnosis and management of the infected total knee replacement: a practical surgical guide.</a> Journal of Experimental Orthopaedics. 8 (1), 14 (2021).</li><li>Parvizi, J., Jacovides, C., Zmistowski, B., Jung, K. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Definition+of+periprosthetic+joint+infection:+Is+there+a+consensus.">Definition of periprosthetic joint infection: Is there a consensus.</a> Clinical Orthopaedics and Related Research. 469 (11), 3022-3030 (2011).</li><li>Karczewski, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Candida+periprosthetic+joint+infections+-+risk+factors+and+outcome+between+albicans+and+non-albicans+strains.">Candida periprosthetic joint infections - risk factors and outcome between albicans and non-albicans strains.</a> International Orthopaedics. 46 (3), 449-456 (2022).</li><li>Cobo, F., Rodriguez-Granger, J., Sampedro, A., Aliaga-Martinez, L., Navarro-Mari, J. 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T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evidence+for+osteocyte-media+ted+bone-matrix+degradation+associated+with+periprosthetic+joint+infection+(PJI).">Evidence for osteocyte-media ted bone-matrix degradation associated with periprosthetic joint infection (PJI).</a> European Cells &amp; Materials. 42, 264-280 (2021).</li><li>Garlito-D&#237;az, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+antifungal-loaded+sol-gel+can+prevent+candida+albicans+prosthetic+joint+infection.">A new antifungal-loaded sol-gel can prevent candida albicans prosthetic joint infection.</a> Antibiotics (Basel). 10 (6), 711 (2021).</li><li>Harro, J. 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The infection caused by the contamination of surgical instruments or the surgical environment during surgery is the major reason for most implant infections24,25,26,27. 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...

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.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
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			<td>0.5 Mactutrius turbidibris</td>
			<td>Shanghai Lujing Technology Co., Ltd</td>
			<td>5106063</td>
			<td></td>
		</tr>
		<tr>
			<td>4 &#176;C refrigerator</td>
			<td>Electrolux (China) Electric Co., Ltd</td>
			<td>ESE6539TA</td>
			<td></td>
		</tr>
		<tr>
			<td>Agar</td>
			<td>Beijing Aoboxing Bio-tech Co., Ltd</td>
			<td>01-023</td>
			<td></td>
		</tr>
		<tr>
			<td>Analytical balances</td>
			<td>Shimadzu</td>
			<td>ATX124</td>
			<td></td>
		</tr>
		<tr>
			<td>Autoclaves Sterilizer</td>
			<td>SANYO</td>
			<td>MLS-3750</td>
			<td></td>
		</tr>
		<tr>
			<td>Carbenicillin</td>
			<td>Amresco</td>
			<td>C0885</td>
			<td></td>
		</tr>
		<tr>
			<td>Eclipse Ci Nikon upright optical microscope&#160;</td>
			<td>Nikon</td>
			<td>Eclipse Ts2-FL</td>
			<td></td>
		</tr>
		<tr>
			<td>Glucose</td>
			<td>Macklin&#160;</td>
			<td>D823520</td>
			<td></td>
		</tr>
		<tr>
			<td>Inoculation ring</td>
			<td>Thermo Scientific</td>
			<td>251586</td>
			<td></td>
		</tr>
		<tr>
			<td>Isoflurane</td>
			<td>RWD</td>
			<td>20210103</td>
			<td></td>
		</tr>
		<tr>
			<td>NaCl</td>
			<td>Xi&#39;an Jingxi Shuanghe Pharmaceutical Co., Ltd</td>
			<td>20180108</td>
			<td></td>
		</tr>
		<tr>
			<td>Paraformaldehyde</td>
			<td>Beyotime Biotechnology</td>
			<td>P0099</td>
			<td></td>
		</tr>
		<tr>
			<td>Peptone</td>
			<td>Beijing Aoboxing Bio-tech Co., Ltd</td>
			<td>01-001</td>
			<td></td>
		</tr>
		<tr>
			<td>RWD R550 multi-channel small animal anesthesia machine&#160;</td>
			<td>RWD</td>
			<td>R550</td>
			<td></td>
		</tr>
		<tr>
			<td>SEM</td>
			<td>Hitachi</td>
			<td>TM-1000</td>
			<td></td>
		</tr>
		<tr>
			<td>Temperature incubator</td>
			<td>Shanghai Zhichu Instrument Co., Ltd</td>
			<td>ZQTY-50N</td>
			<td></td>
		</tr>
		<tr>
			<td>Ultrapure water water generator</td>
			<td>Heal Force</td>
			<td>NW20VF</td>
			<td></td>
		</tr>
		<tr>
			<td>Ultrasound machine</td>
			<td>Do-Chrom</td>
			<td>DS10260D</td>
			<td></td>
		</tr>
		<tr>
			<td>Yeast extract</td>
			<td>Thermo Scientific&#160;Oxoid</td>
			<td>LP0021B</td>
			<td></td>
		</tr>
	</tbody>
</table>

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.

Author Spotlight: Advancing Research on Candida albicans Biofilm-Associated Prosthetic Joint Infections 

A Periprosthetic Joint Candida albicans Infection Model in Mouse

In this study of Candida albicans biofilm-associated peri-prosthetic joint, Candida albicans infection model in mice was constructed, using titanium-nickel wire, commonly used to simulate joint implants. This PJI model is easy to operate, has a high success rate, and is clinically relevant. It will help understanding the prevention and treatment of Candida albicans biofilm-related PJI.Traditional animal models cannot accurately simulate the actual situation of PJI, due to the complex environment surrounding the processes. Candida albicans biofilm-related mouse PJI model, can address the research gap. The establishment of PJI animal model is very important for the research and the development of new drugs or therapeutics for PJI.The Candida albicans biofilm-associated mouse PJI model established in this paper is expected to be an important model for the prevention and treatment of Candida albicans biofilm-associated PJI.

Transferring the samples onto a plate medium and counting colonies after overnight incubation is commonly used to assess the local pathogen load near the lesion22,23. In our study, the microbial culture of liver, kidney, and spleen samples was negative, indicating that the model in this study only led to local infection instead of systemic infection in the mice23.
The SEM images of the implants are shown in <str...

Watch this Scientific Journal Video about Advancing Research on Candida albicans Biofilm-Associated Prosthetic Joint Infections at JoVE.com

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 ...

a-periprosthetic-joint-candida-albicans-infection-model-in-mouse

Research

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Immunology and Infection

Establishing a Candida albicans Biofilm-Associated Periprosthetic Joint Infection (PJI) Mouse Model

Establishing a Candida albicans Biofilm-Associated Periprosthetic Joint Infection (PJI) Mouse Model  

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

454 Views.  Xi’an Jiaotong University.  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.

Establishing a Mouse Model for Candida albicans Biofilm-Related PJI

Summary