Dimorphic Fungal genomes
The dimorphic fungi are phylogenetically related pathogens and include several species: Coccidioides, Paracoccidioides, Blastomyces, Lacazia loboi and Histoplasma. Together, these species are the most common etiologic agents of pulmonary infection by fungi in healthy hosts, causing over one million new infections each year in the United States alone. These fungi exist as a nonvirulent filamentous form in the soil and a budding yeast form (or in the case of Coccidioides, a related spherule/endospore form) in the host pulmonary system. This project aims to determine the unique features of each species, as well as those shared as a pathogenic group.
Dimorphic fungi form a group that is comprised of phylogenetically related pathogens in the Phylum Ascomycota, and includes several species: Coccidioides, Paracoccidioides, Blastomyces, Lacazia loboi and Histoplasma. Together, these species are the most common etiologic agents of pulmonary infection by fungi in healthy hosts, causing over one million new infections each year in the United States alone. A common attribute of these pathogens is the distinct growth conditions associated with temperature dependent alterations in morphological state. These fungi exist as a nonvirulent filamentous form consisting of long chained cells producing asexual spores in the soil and a budding yeast form, or in the case of Coccidioides, a related spherule/endospore form, in the host pulmonary system. Generally, infection of the host with dimorphic fungi typically occurs following disruption of the mycelial cells residing in soil and subsequent inhalation of airborne microconidia, which transform into a parasitic yeast form in the pulmonary alveolar epithelium.
What is Coccidioides?
Coccidioides immitis is an ascomycete soil fungus found in the Central Valley of California, San Diego and Baja California. It is one of a pair of species (the other being C. posadasii) found in the desert regions of North America, Mexico, and scattered areas in South America, particularly Argentina, that causes coccidioidomycosis, also known as "valley fever." In the soil, both Coccidioides species produce hyphae and mitospores, and both are specifically adapted to live in mammals, including humans. When mitospores are inhaled, they enlarge to make spherules, which divide internally to make endospores. One spherule can release thousands of endospores, which, in turn, mature into spherules. No sex is known in either species.
What is Blastomyces?
Blastomyces dermatitidis is the causative agent of blastomycosis, a geographically widespread systemic mycosis of humans and other mammals. Although blastomycosis occurs worldwide, it is most common in North America and is endemic to the Ohio and Mississippi River Valley regions. We have sequenced two genetically tractable, but pathogenetically distinct, strains of Blastomyces dermatitidis. The SLH-14081 strain is a highly virulent, clinical isolate that can cause disease in immunocompetent people. After mild infection, blastomycosis can undergo a prolonged latent period and reactivate in individuals with compromised immune systems, as is the case in AIDS patients. Untreated acute blastomycosis frequently progresses to severe pulmonary disease, with potential for dissemination to other organs, skin and bone. Comparative analysis between the SLH-14081 strain and an avirulent strain, ER-3, provides the opportunity to identify genomic attributes unique to the virulent SLH-14081 strain and therefore, important in blastomycosis.
What is Paracoccidioides brasiliensis?
Paracoccidioides brasiliensis is the causal agent of paracoccidioidomycosis (PCM), one of the most important human systemic mycosis in Latin America (Restrepo et al. 2001). It is estimated that about 10 million people are infected in South America (Brummer et al. 1993). Most of these infections occur in Central and South America, particularly in Brazil, Venezuela, and Colombia. The annual incidence rate in Brazil is 10-30 infections per million inhabitants, and the mean mortality rate is 1.4 per million per year (Restrepo et al. 2001). PCM is a granulomatous disease that produces a primary pulmonary infection. In addition, disseminated forms may also be observed. The reticuloendothelial system, skin, mucous membranes and lymph nodes are frequently affected in cases of disseminated disease.
What is Histoplasma capsulatum?
Histoplasma capsulatum is the most common cause of fungal respiratory infections (histoplasmosis) in the world. While most infections are mild, 10% of cases result in life-threatening complications such as inflammation of the pericardium and fibrosis of major blood vessels (Durkin, Kohler et al. 2001). In addition, some African H. capsulatum isolates cause a distinct disease, African histoplasmosis, that is characterized by cutaneous and subcutaneous lesions in the bone (Jones and Goodwin., 1981). Once infected, a latent infection may be reactivated. Histoplasma poses a particular threat to the elderly and to immunocompromised patients (Rachid, Rezende et al. 2003).
Restrepo et al. The habitat of Paracoccidioides brasiliensis: how far from solving the riddle? Med Mycol. 2001
Rachid, A., L.S. Rezende et al. (2003). A case study of disseminated histoplasmosis linked to common variable immunodeficiency. Braz J Infect Dis. 7(4):268-272.
Woods, J.P. (2003). Knocking on the right door and making a comfortable home: Histoplasma capsulatum intracellular pathogenesis. Curr Opin Microbiol 6: 327-31.
Individual Group Project Links
This sequencing project was supported by the National Institute of Allergy and Infectious Disease, National Institutes of Health funded Genome Sequencing Center for Infectious Diseases at the Broad Institute.