Virulence factors of Cryptococcus neoformans

Abstract

Cryptococcus neoformans is an encapsulated yeast which causes cryptococcosis, a disease typified by an initial pulmonary infection which can disseminate to cause a life threatening meningoencephalitis. Although the disease may occur in individuals who show no evidence of immunosuppression it has had it most significant impact as an infection in patients with AIDS. Research into the potential virulence factors of this yeast has recently attracted particular attention. Capsule synthesis has been the focus of most interest and it is now established as a major virulence determinant. The mechanisms by which the capsule and capsular material effect the immune response have now largely been elucidated, and the genes underlying capsular synthesis are now under investigation. The isolation of mutants incapable of melanogenesis have implicated this process in the pathogenesis of C. neoformans infections, and evidence suggests that the production of melanin protects the yeast against oxidant induced damage. There is also some genetic evidence for the potential involvement of temperature tolerance and mating types in the virulence of this encapsulated yeast. The roles of other potential C. neoformans virulence determinants are more speculative; these include proteinase production, release of polyol metabolites, interaction with hormones, adherence and production of mannoproteins. The involvement of housekeeping enzyme systems in the maintenance of infection by C. neoformans is now also under active investigation.