A murine model of Cryptococcus gattii meningoencephalitis

George Richard Thompson, Nathan P. Wiederhold, Laura K. Najvar, Rosie Bocanegra, William R. Kirkpatrick, John R. Graybill, Thomas F. Patterson

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numberdks060
Pages (from-to)1432-1438
Number of pages7
JournalJournal of Antimicrobial Chemotherapy
Volume67
Issue number6
DOIs
StatePublished - Jun 2012

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Keywords

  • C. gattii
  • Cryptococcal meningoencephalitis
  • Cryptococcus neoformans
  • Fluconazole
  • Posaconazole

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Thompson, G. R., Wiederhold, N. P., Najvar, L. K., Bocanegra, R., Kirkpatrick, W. R., Graybill, J. R., & Patterson, T. F. (2012). A murine model of Cryptococcus gattii meningoencephalitis. Journal of Antimicrobial Chemotherapy, 67(6), 1432-1438. [dks060]. https://doi.org/10.1093/jac/dks060