Addition of unsaturated fatty acids down-modulates heat shock gene expression and produces attenuated strains in the fungus Histoplasma capsulatum

Histoplasma capsulatum is the causative agent of histoplasmosis, a systemic fungal disease world-wide in occurrence and the most common respiratory mycotic infection affecting humans and animals. This organism, that consists of a pathogenic yeast phase present in human tissue and a saprobic mycelial phase found in soil, represents at a molecular level, the most extensively studied of the dimorphic pathogenic fungi (Maresca and Kobayashi, 1989). In culture, the transition from one phase to the other can be triggered reversibly by shifting the temperature of incubation between 25° (mycelia) and 37°C (yeast). This implies that each growth phase is an adaptation to two remarkably different environments. Therefore, it is likely that the temperature-induced phase transition and the events in the establishment of infection are intimately interrelated and, unlike the case in higher eukaryotes, the differentiation process in dimorphic fungi represents an adaptation to a new environment. In fact, the organism must face challenges that may not be strictly related to dimorphism to proceed towards phase transition (e.g., higher temperature, different redox potential and nutrients, presence of new degradative enzymes, etc.).