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Urease as a virulence factor in experimental cryptococcosis.
G M Cox1, J Mukherjee, G T Cole
1Division of Infectious Disease, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. cox00005@mc.duke.edu
Infection and Immunity
|January 20, 2000
Summary
Urease plays a role in cryptococcosis pathogenesis. A urease-deficient Cryptococcus neoformans mutant showed reduced virulence in mouse models, suggesting urease is a potential therapeutic target.
Area of Science:
- Mycology
- Pathogenesis
- Molecular Biology
Background:
- Urease is a virulence factor in some bacteria.
- Cryptococcus neoformans, a pathogenic fungus, produces significant urease.
- The role of urease in cryptococcosis pathogenesis requires investigation.
Purpose of the Study:
- To investigate the role of urease in the pathogenesis of cryptococcosis.
- To clone and disrupt the URE1 gene in Cryptococcus neoformans.
- To assess the virulence of a ure1 mutant in various infection models.
Main Methods:
- Cloning and sequencing of the C. neoformans URE1 gene.
- Gene disruption to create ure1 mutant strains.
- In vitro characterization and in vivo infection models (murine intravenous, inhalational; rabbit intracisternal).
Main Results:
- Ure1 mutant strains exhibited similar in vitro growth, phenoloxidase activity, and capsule size to wild-type.
- No significant difference in cerebrospinal fluid fungal burden in rabbit model.
- Mice infected with ure1 mutant showed increased survival in systemic infection models.
- Complementation restored virulence, confirming URE1's role.
Conclusions:
- Urease activity is implicated in the pathogenesis of cryptococcosis.
- The significance of urease may be specific to the fungal species and infection site.
- Targeting urease could be a strategy for treating cryptococcosis.