Insights into Fungal Morphogenesis and Immune Evasion

F or endemic dimorphic fungi, switching between different morphologies is crucial for pathogenesis. These ascomycetes, which include Blastomyces dermatitidis, Histoplasma capsulatum, Coccidioides immitis, Coccidioides posadasii, Paracoccidioides brasiliensis, Sporothrix schenckii, and Penicillium marneffei, grow as mycelia that produce conidia or, in the case of Coccidioides spp., arthroconidia, when in soil or comparable environments (Fig. 1). Dimorphic fungi typically are restricted to specific ecological niches. For example, Coccidioides spp. thrive in the alkaline-rich lower sonoran zone in the U.S. Southwest, whereas H. capsulatum and B. dermatitidis dwell in moist, acidic soils of the Midwest and Southeast. When those environments are disrupted, the conidia and mycelial fragments can be aerosolized, making infectious particles available for mammalian hosts to inhale. Once situated in lungs, the fungi become pathogenic yeast or, in the case of Coccidioides spp., spherules that contain endospores (Fig. 1). These dimorphic fungi are primary pathogens that infect both immunocompetent and immuncompromised hosts. Although infections sometimes remain subclinical, symptoms may develop to include pneumonia, acute respiratory distress syndrome (ARDS), and disseminated disease, which can affect multiple organ systems. The extent and severity of infection are influenced by the inoculum size and the integrity of the host immune system. The endemic dimorphic fungi must switch from a mold to a yeast form to survive in human and other mammalian hosts, in part because this change enables them to evade host immune defenses. This phase transition comes with characteristic changes in the cell wall, membrane lipids, intracellular signaling, and gene expression. When locked in the mycelial phase by biochemical or genetic means, these would-be pathogens fail to cause disease. The mechanisms that enable endemic dimorphic fungi to adapt and survive within the mammalian host are of particular interest to us.