Abstract
This review summarizes the biology of Histoplasma capsulatum in relation to a wide variety of corresponding pathologies in histoplasmosis. Features of these disease syndromes can be explained in part by natural variations within the fungal population and adaptations made by individual organisms to specific environments. H. capsulatum grows as mycelia and conidia in the soil; once inhaled, the organism undergoes a dramatic morphological and physiological conversion to a yeast form. The yeasts proliferate within the phagolysosomes of macrophages, using a variety of specific strategies for intracellular survival. Even avirulent strains or variants are able to avoid being killed by macrophages and instead establish inapparent or persistent infections. The ingested avirulent organisms assume enlarged shapes similar in appearance to those seen in histological sections of tissues from patients with histoplasmosis. Respiratory tract epithelial cells also appear to play a role in persistence: within them yeasts undergo phenotypic switching akin to the phase variation observed in other pathogens. This particular change involves the loss or modification of cell wall alpha-(1,3)-glucan, which is also correlated with the spontaneous appearance of avirulent variants. The repertoire of adaptive responses and natural variations within this species probably evolved from the need to adjust to a wide range of dynamic environments. In combination with the immune status of the host, these characteristics of H. capsulatum appear to influence the epidemiology, extent, and persistence of histoplasmosis.