The gene encoding phosphoribosylaminoimidazole carboxylase (ADE2) is essential for growth of Cryptococcus neoformans in cerebrospinal fluid.

Journal Article (Journal Article)

A cryptococcal meningitis model in corticosteroid-treated rabbits was used to assess the requirement for the phosphoribosylaminoimidazole gene (ADE2) for virulence of Cryptococcus neoformans. A wild-type strain (H99), an ade2 auxotroph of H99 (M001), and a randomly selected prototrophic transformant of M001 (M001.1c) which had received the cloned ADE2 cDNA copy were inoculated intrathecally into immunosuppressed rabbits. While M001 was avirulent in the central nervous system model, virulence was completely restored to wild-type pathogenicity in the prototrophic transformant. This study identifies the pathogenic importance of an endogenous adenine pathway in this yeast and confirms that purine biosynthesis is a potential target for antifungal therapy. It also demonstrates that the virulence of C. neoformans can be molecularly changed and detected within a clinically relevant animal model.

Full Text

Duke Authors

Cited Authors

  • Perfect, JR; Toffaletti, DL; Rude, TH

Published Date

  • October 1993

Published In

Volume / Issue

  • 61 / 10

Start / End Page

  • 4446 - 4451

PubMed ID

  • 8406836

Pubmed Central ID

  • PMC281178

International Standard Serial Number (ISSN)

  • 0019-9567

Digital Object Identifier (DOI)

  • 10.1128/iai.61.10.4446-4451.1993


  • eng

Conference Location

  • United States