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Published on: December 8, 2011
A modified method for experimental candidosis in mice avoiding lethality
Abstract:
A model is presented which selected one out of 150 Candida albicans strains for the evaluation of antifungal agents. The mice were inoculated with 6 x 10(5) CFU of strain 352 into the tail vein. The strain has a moderate phospholipase B (PLB) activity in vitro and was originally isolated from a stool sample from a patient in an intensive care unit. This infection leads to very little suffering in the infected animals during the 6-day observation period. Kidney counts at day 5 after infection can give a first indication for a possible fungistatic mechanism. Possible interesting drugs can then be evaluated by a second set of experiments using a longer observation time to investigate the compounds for fungicidal properties. The model suggests that screening for systemic antifungals by avoiding lethality of mice in the first place can be done.
Insights
This study presents a new mouse model for evaluating antifungal drugs against Candida albicans. The model uses a specific strain to assess drug efficacy without causing excessive animal suffering, aiding in the discovery of systemic antifungals.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Pharmacology
Background:
- Candida albicans is a significant opportunistic fungal pathogen.
- Developing effective systemic antifungal agents is crucial for treating invasive candidiasis.
- Existing animal models for antifungal drug screening often involve high mortality rates.
Purpose of the Study:
- To develop and validate a novel mouse model for screening systemic antifungal agents.
- To utilize a specific Candida albicans strain with moderate phospholipase B activity for infection modeling.
- To establish a screening approach that prioritizes reduced animal distress and avoids early lethality.
Main Methods:
- Selection of one Candida albicans strain (352) from 150 isolates.
- Intravenous inoculation of mice with 6 x 10(5) CFU of strain 352.
- Assessment of fungal burden in kidneys at day 5 post-infection.
- Evaluation of fungistatic and fungicidal properties of antifungal agents through extended observation periods.
Main Results:
- The selected Candida albicans strain caused a mild infection with minimal animal suffering over a 6-day period.
- Kidney fungal counts at day 5 provided an initial indicator of fungistatic drug activity.
- The model allows for subsequent experiments to determine fungicidal properties of promising compounds.
Conclusions:
- A validated mouse model for screening systemic antifungal agents has been established.
- This model enables efficient evaluation of antifungal drug efficacy by minimizing animal mortality in initial screenings.
- The approach facilitates the identification of potential drug candidates for invasive fungal infections.
