Background Introduction
Candida albicans is a type of opportunistic pathogenic fungus. It is a common symbiotic bacterium in the human microbiome (particularly in the oral cavity, gastrointestinal tract, and reproductive tract), usually coexisting peacefully with the immune system in a healthy human body and not causing diseases. However, when the local or systemic immunity of the host (the human body) declines, or the balance of the bacterial community is disrupted, Candida albicans will proliferate excessively and change its morphology (from yeast form to a more invasive filamentous form), thereby causing infection, which is known as “candidiasis”.
Candida albicans infection is one of the most common hospital-acquired infections worldwide. The incidence rate and the number of high-risk individuals are continuously increasing, mainly due to advancements in medical technology (such as the use of broad-spectrum antibiotics, immunosuppressants, and invasive procedures) and the growing number of individuals with weakened immunity (such as cancer patients, organ transplant recipients, and the elderly).
Clinical infection types of Candida albicans
| Infection type | High-risk population | Common infection sites / manifestations | Clinical features and challenges |
| Mucosal infections (such as vulvovaginal inflammation, pharyngolaryngeal inflammation) | Healthy individuals and those with low immunity | Vaginal and oral mucous membranes | The most common manifestation is abnormal discharge. |
| Invasive infections (candidemia, deep organ infections) | Those with severe conditions, immunosuppression, or who have catheters inserted | Blood flow, abdominal cavity, organs | The mortality rate is high (close to 40%) and the treatment is complex, with a prominent problem of drug resistance. |
Current Status and Challenges of Clinical Treatment
01Main drug categories
The commonly used ones include azoles (such as fluconazole), echinocandins (such as caspofungin), polyenes (such as amphotericin B), and flucytosine. Among them, echinocandins (such as caspofungin) are often recommended by guidelines as the initial preferred drugs for invasive candidiasis (such as candidemia) due to their efficacy and safety.
02The issue of drug resistance during treatment
Drug resistance, especially resistance to azole drugs, is one of the most challenging clinical problems at present. Studies have shown that Candida albicans can accelerate the evolution of drug resistance through special mechanisms such as protein mis-translation.
Common animal models used in preclinical efficacy studies
| Types of animal models | Infection type | Model characteristics | Drug efficacy assessment |
| Mouse systemic infection model | Invasive sepsis | The mortality rate is high, and there is a high bacterial load in all organs throughout the body. | Mortality protection, inhibition of bacterial load in major organs, etc. |
| Mouse lung infection model | Fungal pneumonia | The lungs have a high bacterial load and acute damage, and the mortality rate is high for those with high-dose infections. | Improvement in lung bacterial load and pathological changes, as well as mortality protection, etc. |
| Mouse model of reproductive tract infection | Fungal vaginitis | Increased vaginal discharge, inflammatory infiltration of vaginal tissues, and fungal infection | Reproductive tract bacterial load, improvement of reproductive tract pathology, etc. |
KCI•KMQ Anti-Infection Vaccine and Drug Research and Development Platform
KCI•KMQ has established a dual-qualified BSL-2 and ABSL-2 laboratory, providing a research service platform for over 100 types of pathogenic microorganisms (bacteria, viruses and fungi), including those required for the development and research of anti-infective drugs for humans, veterinary drugs, and pet drugs. The BSL-2 laboratory covers an area of approximately 200 square meters, including cells, viruses and bacteria; the ABSL-2 laboratory covers an area of approximately 1,000 square meters, with a small animal laboratory of 300 square meters and a large animal laboratory of 700 square meters. Through years of internal research and external services, KCI•KMQ has successfully established various infectious animal models for viruses, bacteria and fungi, and is committed to providing high-quality pharmacological and pharmacodynamic evaluation services for customers, mainly including:
（1）In vitro anti-infective efficacy test: Antiviral effect – EC50/CC50 detection; MIC drug sensitivity test; FIC determination; Effects on biological characteristics, etc.
（2）Vaccine in vivo immunogenicity test: neutralization test, hemagglutination inhibition test, cellular immunity, etc.
（3）Animal protective toxicity tests: Vaccines, antiviral drugs;
（4）Infectious animal experiments.
Case Sharing of the Mouse Model of Candida Albicans Infection
01 Mouse model of Streptococcus pneumoniae infection
Testing content
• Weight and survival period monitoring
• Bacterial load in the lungs
• Lung HE pathological staining
Data sharing
• Animal weight and lifespan
Figure 1: Statistics of Animal Weight and Lifespan
Compared with the solvent group, both amphotericin B inhalation administration via the trachea and tail vein injection administration could significantly protect the animals against weight loss and mortality. Among them, the effect of inhalation administration via the trachea was more prominent.
• Bacterial load in the lungs and evaluation of lung pathology
Figure 2: Bacterial load in the lungs and HE pathological staining
The lungs of the solvent group had a higher white candida load, and the lungs showed severe pathological changes such as severe necrosis, hemorrhage, edema, and inflammatory exudation. Compared with the solvent group, both administration methods of amphotericin B could significantly reduce the bacterial load in the lungs and the pathological score. Among them, the intratracheal instillation administration method was more effective.
02 Mouse model of septicemia caused by Streptococcus pneumoniae
Testing content
• Animal weight
• The bacterial load in the kidneys
Data sharing
• The lifespan of animals and the bacterial load in their kidneys
Figure 1: Animal lifespan and kidney bacterial load
Compared with the solvent group, the mortality rate and the bacterial load in the kidneys of the animals in the low and high dose groups of the test substance were significantly reduced.
03 Mouse model of vulvar candidiasis
Testing content
• Clinical observation of the reproductive tract
• Detection of bacterial load in vaginal irrigation solution
• Analysis of vaginal tissue by HE staining and PAS staining
Data sharing
• Vaginal clinical observation and detection of bacterial load in vaginal lavage fluid
Figure 1: Vaginal clinical observation and detection of bacterial load in vaginal irrigation fluid
After the model was established, the vaginal purulent discharge increased and became red and swollen.
The vaginal lavage fluid showed consistently high levels of Candida albicans (＞10^4 CFU/mL) at all time points examined.
• Pathological changes in the vaginal wall and cervical fornix – HE staining and PAS staining
Figure 2: HE staining of the reproductive tract
Figure 3: PAS staining of the reproductive tract
After the model infection, a large number of inflammatory cells were observed infiltrating the vaginal secretions, vaginal walls, cervical fornix mucosal epithelial layer and the submucosa of the vagina, as well as the colonization and growth of Candida albicans.
