Researchers have estimated that there were about one million infections and a half a million deaths from HIV-related cryptococcal meningitis worldwide in 2006. The findings published in the February 20th edition of the journal AIDS also show that sub-Saharan Africa had the highest global burden of cryptococcal meningitis among people living with HIV. The scientists (led by Benjamin J. Park of the US Centers for Disease Control) did the study because although although cryptococcal meningitis is one of the most widely reported HIV-related opportunistic infections, the global burden is unknown In regions with higher HIV burdens, particularly sub-Saharan Africa, cryptococcal meningitis has been reported to be on the increase (more than any other type of meningitis).

The fungus Cryptococcus neoformans is a leading cause of mortality and morbidity among HIV-infected individuals. We utilized the completed genome sequence and optimized methods for homologous DNA replacement using high-velocity particle bombardment to engineer 1201 gene knockout mutants. We screened this resource in vivo for proliferation in murine lung tissue and in vitro for three well-recognized virulence attributes—polysaccharide capsule formation, melanization, and growth at body temperature. We identified dozens of previously uncharacterized genes that affect these known attributes as well as 40 infectivity mutants without obvious defects in these traits. The latter mutants affect predicted regulatory factors, secreted proteins, and immune-related factors, and represent powerful tools for elucidating novel virulence mechanisms. In particular, we describe a GATA family transcription factor that inhibits phagocytosis by murine macrophages independently of the capsule, indicating a previously unknown mechanism of innate immune modulation.