Abstract
In the past half century Cryptococcus neoformans emerged as a major human pathogen leading the World Health Organization to place it among its top four critical priority group. C. neoformans is common in the environment resulting in widespread human exposure but disease in immunocompetent hosts is rare. The fungus is endowed with powerful virulence factors that allow it to resist immunological mechanisms for clearance. Despite this, the fungus does not appear to have any need for an animal host in its life cycle and consequently these virulence factors are traits selected for environmental survival that function accidentally as enablers of virulence in susceptible hosts. Considerable progress has been made in understanding its life cycle, ecology, pathogenicity mechanisms, and antigenic composition for vaccine design. In this essay, the problem of cryptococcal pathogenesis and virulence is approached from the viewpoint of considering these processes in the context of its environment and ecology.