Histoplasma Genome Project

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). The comparative Histoplasma capsulatum project is funded by NIAID through the "Comparative Genomics of Coccidioides and other Pathogenic Dimorphic Fungi" whitepaper. This project aims to examine diversity between Histoplasma capsulatum strains and determine the common and unique features among the larger group of dimorphic fungal pathogens.

Project Information

The Histoplasma capsulatum sequencing project is part of the Broad Institute Fungal Genome Initiative. Its goal was to release an annotated assembly with 4X genome sequence coverage for Histoplasma capsulatum class NAmI strain WU24, as well as for the African clade (H143) strain that causes respiratory histoplasmosis. We also released an annotated assembly with 8X genome sequence coverage for the African clade (H88) strain, the cause of African histoplasmosis. We generated a 4X genome sequence coverage of the Histoplasma capsulatum G186AR genome and together with the ~6X coverage provided by the Genome Sequencing Center at Washington University in St. Louis, built a high quality assembly that is presently being annotated by our team. Anita Sil's laboratory at the University of California San Francisco and William Goldman's laboratory at Washington University School of Medicine provided the genomic DNA for the Histoplasma sequencing project.

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).
Molecular characterization has shown that a number of fungi collectively known as H. capsulatum actually comprises seven phylogenetic species. There are two discrete phylogenetic species in Northern America: Histoplasma class I (NAm I) and Histoplasma class II (NAm II) (Kasuga, White et al. 2003). Sequence analysis shows that the two Northern American phylogenetic species are as distant from each other as from any other Histoplasma clade, which radiated 3-30 million years ago (Kasuga, White et al. 2003). These strains have notable phenotypic differences, such as alterations in cell wall components. In addition, they also exhibit key differences in the extent of virulence in the host. While the NAm I strains are chiefly isolated only from AIDS patients, NAm II strains infect otherwise healthy individuals.
H. capsulatum sequencing is underway at Washington University for NAm II. Sequencing the closely related NAm I strain will clarify the genomic basis for the difference in virulence and interactions with the host immune system. Comparative genomic analysis of these strains with the Latin American (G186AR) and African clade (H143 and H88) strains should allow the identification of genes that are selected in diverse geographical environments, as well as the identification of rapidly evolving genes. These studies will diversify and strengthen our understanding of H. capsulatum biology, and will provide an additional richness to the dimorphic analysis as a whole.


References
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.
Durkin M, et al. (2001) Chronic infection and reactivation in a pulmonary challenge model of histoplasmosis. J Infect Dis. 183(12):1822-4.
Kasuga T, et al.(2003) Phylogeography of the fungal pathogen Histoplasma capsulatum. Mol Ecol. 12(12):3383-401.
Jones RC, and Goodwin. RA Jr., (1981). Histoplasmosis of bone. Am J Med. 1981 Apr;70(4):864-6.

Data access

The assembled and annoated genomes of Histoplasma are availabe in NCBI via the following links:

Histoplasma capsulatum H143

Histoplasma capsulatum H88

Histoplasma capsulatum G186AR

Histoplasma capsulatum NAm1

Histoplasma capsulatum G217B

 

Data files formerly available on this website can be accessed on our fungal ftp site.