Aimless mutants of Cryptococcus neoformans: failure to disseminate.

The pathogenic fungus Cryptococcus neoformans exhibits a striking propensity to cause central nervous system (CNS) disease in people with HIV/AIDS. Given that cryptococcal infections are generally initiated by pulmonary colonization, dissemination requires that the fungus withstand phagocytic killing, cross the alveolar-capillary interface in the lung, survive in the circulatory system and breach the blood-brain barrier. We know little about the molecular mechanisms underlying dissemination, but there is a rapidly growing list of mutants that fail to cause CNS disease. These mutants reveal a remarkable diversity of functions and therefore illustrate the complexity of the cryptococcal-host interaction. The challenge now is to extend the analysis of these mutants to acquire a detailed understanding of each step in dissemination.