Though Histoplasma is dimorphic, little is known about the genes that regulate the transformation from one stage to another. When inhaled from contaminated soil, the spores germinate in the lungs, where the fungi are ingested by macrophages, in which they multiply. A lesion develops that resembles primary tuberculosis. The yeast-like form found in infected lungs is not transmissible person to person. While most respiratory infections with the organism are mild, ten percent of cases result in life-threatening complications such as inflammation of the pericardium and fibrosis of major blood vessels. Once infected, a latent infection may be re-activated. Histoplasma poses a particular threat to the elderly and to immunocompromised patients such as those infected with HIV, or to organ transplant recipients undergoing immunosuppressant drug therapy.
Histoplasma is a dimorphic fungus. The mold or mycelial form exists in soil contaminated with droppings of bats or birds such as starlings or chickens, where it absorbs nutrients from dead organic matter and produces infectious spores. When these spores are inhaled and encounter the warm moist environment of the lungs, they undergo a transformation to the yeast or parasitic form. Histoplasma capsulatum is the most common cause of fungal respiratory infections in the world (histoplasmosis), and it is endemic to the Ohio and Mississippi River Valleys of the United States.
A fosmid fingerprint map of the Histoplasma capsulatum genome was generated and improved draft sequence of the G217B strain from combined whole genome shotgun and fosmid-specific reads was produced. For comparative purposes, a two-fold sequence coverage of G186AR, a virulent strain that is commonly used in laboratory studies, also was generated. Those two assemblies were annotated and the predicted genes were used to develop 70mer microarays in order to study gene expression differences between the mold and yeast forms. An ACE database is being maintained that merges sequence and mapping information with sequence-based gene predictions in a graphical interface accessible through this web site. The collaborators for this project were the University of California at San Francisco and the Department of Molecular Microbiology here at Washington University. Funds for this project were provided by the National Institute for Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH).