A murine model of Cryptococcus gattii meningoencephalitis
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Published on: November 5, 2019
George R Thompson1, Nathan P Wiederhold, Laura K Najvar
1Department of Medical Microbiology and Immunology and Department of Internal Medicine the Division of Infectious Diseases, The University of California Davis, Davis, CA, USA. grthompson@ucdavis.edu
Objectives:
Meningoencephalitis caused by Cryptococcus gattii is associated with significant morbidity and the need for aggressive therapy, and often necessitates neurosurgical intervention. We adapted a previously described murine model of cryptococcal meningoencephalitis due to Cryptococcus neoformans to that caused by C. gattii.
Methods:
Mice were inoculated intracranially with either C. gattii (genotype VGIIa) or C. neoformans. In virulence studies, different C. gattii infecting inocula were compared with a fixed inoculum of C. neoformans, and differences were assessed by survival, brain tissue fungal burden, serum antigen titres and histopathological changes within brain tissue. For treatment, fluconazole or posaconazole (10 mg/kg orally twice daily) was initiated 24 h post-inoculation.
Results:
C. gattii was more virulent than C. neoformans, as evident by shorter median survival, earlier histopathological changes and higher serum antigen titres. However, no differences in fungal burden or dissemination to other organs were observed among the various groups. In treatment studies, both fluconazole and posaconazole improved the median survival of mice infected with either species. However, neither regimen improved the percentage of animals surviving to the predetermined study endpoint.
Conclusions:
These results demonstrate the virulence of C. gattii meningoencephalitis and the potential of this model for the assessment of new treatment strategies.
Insights
Cryptococcus gattii causes severe meningoencephalitis in mice, proving more virulent than Cryptococcus neoformans. Antifungal treatments improved survival but did not prevent mortality in this new model.
Area of Science:
- Mycology
- Infectious Diseases
- Neuroscience
Background:
- Cryptococcus gattii causes severe meningoencephalitis requiring aggressive treatment.
- A murine model for Cryptococcus neoformans meningoencephalitis was adapted for C. gattii.
Purpose of the Study:
- To adapt a murine model for C. gattii meningoencephalitis.
- To compare the virulence of C. gattii and C. neoformans in mice.
- To evaluate antifungal treatment efficacy in this model.
Main Methods:
- Mice were intracranially inoculated with C. gattii (VGIIa) or C. neoformans.
- Virulence was assessed by survival, fungal burden, antigen titers, and histopathology.
- Fluconazole and posaconazole were administered 24 hours post-inoculation.
Main Results:
- C. gattii demonstrated higher virulence than C. neoformans, indicated by shorter survival and increased histopathological changes.
- No significant differences in fungal burden or dissemination were observed.
- Antifungal treatment improved median survival but not overall survival rates.
Conclusions:
- The adapted model effectively demonstrates the virulence of C. gattii meningoencephalitis.
- This model holds potential for evaluating novel therapeutic strategies against C. gattii infections.
