Abstract
Cryptococcus neoformans is an environmental fungal pathogen that can cause devastating infection in the central nervous system. The important issues in the pathogenesis of cryptococcal brain infection is how C. neoformans enters the brain and then adopt to the brain oxygen level which is significantly lower than the optimum level (21%) for the growth of the fungus. In order to address the mechanism by which C. neoformans crosses the blood-brain barrier (BBB), we used an in vitro model of the human BBB. We demonstrated that C. neoformans invades the brain by transcellular crossing of the endothelium of the BBB. To investigate the genetic basis for the crossing of BBB and adaptation to the low oxygen conditions in the brain, we performed genetic screening of mutant strains that showed defects in crossing the BBB and/or growth under low oxygen conditions. Molecular dissecting of the mutated genes and the virulence of the mutants in experimental animas showed that the ability to grow under low oxygen conditions is an important pathobiological factor of C. neoformans.
