We are interested in the molecular mechanisms that underlie the virulence of the respiratory fungal pathogen Histoplasma capsulatum, the causative agent of histoplasmosis. In particular, we study the interaction between Histoplasma yeasts and their primary host cell, the mammalian macrophage. Unlike opportunistic pathogens, Histoplasma can cause disease in immunocompetent hosts, implying that Histoplasma has specific mechanisms designed to promote pathogenesis. One of these mechanisms is the elaboration of a cell wall polysaccharide, alpha-(1,3)-glucan, on the cell surface, which effectively masks the underlying immunostimulatory beta-glucans from detection by the host. With a genome harboring an estimated 10,000 genes, we have only scratched the surface in defining the genes important for Histoplasma virulence
