Jillian Freese, Ph.D.
Histoplasma capsulatum
Fungal pathogens are globally distributed and infect hundreds of thousands of people each year. One such pathogen, Histoplasma capsulatum, is the causative agent of histoplasmosis, a respiratory disease that infects tens of thousands of people in the United States each year. In the United States, Histoplasma can be found in the eastern and central states, especially in the Ohio and Mississippi River Valleys. Histoplasma has also been found in Africa, Asia, Central America, and South America. People are infected after inhaling the microscopic asexual spores (conidia) of Histoplasma that are aerosolized after contaminated soil is disturbed. Histoplasmosis causes mild flu-like symptoms for most but can cause a life-threatening systemic disease for immunocompromised individuals or those who inhale a large number of infectious particles. The moderate symptoms experienced by many has resulted in an underestimation of Histoplasma infection rate.
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For more information on histoplasmosis:
https://www.cdc.gov/fungal/diseases/histoplasmosis/index.html
Many species of fungi are dimorphic, meaning that they can switch their vegetative morphology between unicellular yeast and multicellular hyphal (filamentous) forms. Several of these species are thermally dimorphic, where the morphological change is triggered by a change in temperature.
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Histoplasma infections begin following the inhalation of conidia (asexual spores) or hyphal fragments. The temperature change between their natural environment and mammalian lungs initiates the transition from multicellular hyphae and conidia to single-celled yeasts. Fungal cells are detected by the mammalian immune system and are taken up by alveolar macrophages. Macrophages are large white blood cells that recognize and engulf foreign particles in order to digest them in an acidic environment. Histoplasma subverts the mammalian immune system by neutralizing the acidic environment in macrophages, which prevents their digestion and allows them to divide and spread throughout the host.
Histoplasma capsulatum filaments
Histoplasma capsulatum yeast
My research aims to understand the environmental variables and genes that govern the Histoplasma transition from conidia to yeast and from conidia to mycelia. Temperature is known to initiate this transition in the laboratory, but other environmental cues are believed to play a role in the morphological switch. The ability to sense environmental changes like temperature, pH, and nutrient availability informs the pathogen about host proximity, initiating a cascade that culminates in the infection of a host. By concentrating on conidial development, my research aims to identify the developmental patterns and regulatory mechanisms associated with Histoplasma morphology and virulence in response to environmental conditions. Results from these studies will be used to generate better models for Histoplasma spread and virulence risk for endemic and new populations as well as identify targets and test therapeutic treatments that will combat Histoplasma infections.