The Cell Biology of Virulence – Lessons from the Pathogenic Fungus Cryptococcus neoformans

Cryptococcus neoformans is a yeast-like fungus that is a major cause of morbidity and mortality in patients with cell-mediated immune defects. Pathogenic strains of C. neoformans are thermotolerant, growing well at mammalian host temperature, and produce a large polysaccharide capsule that is antiphagocytic and immunomodulatory. Also correlated with pathogenicity is the ability to produce melanin pigments, a trait that results from expression of the multi-copper oxidase, laccase. Since the laccase of C. neoformans was purified and its corresponding gene identified, much effort has been placed on understanding factors that affect the production of laccase at the level of transcription, posttranslational modification and trafficking. Our study of laccase has led to the development of tools with which to study the expression of processes essential to cryptococcal virulence, allowing cell biology to inform our understanding of cryptococcal pathogenesis. In this report we detail the development of tools for the study of the cell biology of C. neoformans during mammalian infection, and how these tools are being used to investigate the virulence of this important fungal pathogen