Pathogenesis Mechanisms of Histoplasma capsulatum
Chad A. Rappleye
from: Human Pathogenic Fungi: Molecular Biology and Pathogenic Mechanisms (Edited by: Derek J. Sullivan and Gary P. Moran). Caister Academic Press, U.K. (2014)
The dimorphic fungal pathogen Histoplasma capsulatum causes respiratory and systemic disease in both immunocompromised and immunocompetent individuals. In mammalian hosts, Histoplasma grows as pathogenic yeasts which survive and replicate within phagocytes. Genetic studies have Identified a signaling kinase and 3 transcription factors factors that regulate the thermally-induced yeast-phase differentiation process. The mechanisms that facilitate Histoplasma pathogenesis (summarized in Figure 11.1) centre on three primary tasks facing intracellular pathogens: (1) concealment of molecular signatures to avoid detection by phagocytes and activation of immune defenses, (2) detoxification of antimicrobial defence molecules produced by phagocytes, and (3) acquisition of essential nutrients for growth and replication within the nutrient-limited phagosome. Demonstrated virulence factors accomplishing these required aspects of pathogenesis include synthesis of α-glucan which masks immunostimulatory yeast cell wall β-glucans, production and secretion of antioxidant molecules (extracellular superoxide dismutase and catalase) to defend specifically against phagocyte-derived reactive oxygen, and secretion of multiple factors for iron acquisition (siderophores and iron reductases). In addition, Histoplasma yeasts secrete several novel factors with undefined functions but which are likely linked to pathogenesis by virtue of their specific expression only by pathogenic-phase cells and their extracellular localization. Together, these mechanisms enable Histoplasma yeasts to successfully establish infections in spite of fully functional immune defences of the host read more ...