Histoplasma capsulatum Database

Histoplasma capsulatum NAm1

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.

Citations

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, Kohler S, Schnizlein-Bick C, LeMonte A, Connolly P, Goldberg J, Garringer T, Wheat LJ. (2001) Chronic infection and reactivation in a pulmonary challenge model of histoplasmosis. J Infect Dis. 183(12):1822-4.

Kasuga T, White TJ, Koenig G, McEwen J, Restrepo A, Castaneda E, Da Silva Lacaz C, Heins-Vaccari EM, De Freitas RS, Zancope-Oliveira RM, Qin Z, Negroni R, Carter DA, Mikami Y, Tamura M, Taylor ML, Miller GF, Poonwan N, Taylor JW.(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.

Project Information

The Histoplasma capsulatum sequencing project is part of the Broad Institute Fungal Genome Initiative. Its goal is 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 aim to release an annotated assembly with 8X genome sequence coverage for the African clade (H88) strain, the cause of African histoplasmosis. We have 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. Dr. Anita Sil?s laboratory at the University of California San Francisco and Dr. Goldman's laboratory at Washington University School of Medicine provided the genomic DNA for the Histoplasma sequencing project.

Our specific aims are as follows:

  • Generate and assemble sequence reads yielding 4X coverage of the H. capsulatum H143 genome and 8X coverage of the H. capsulatum H88 genome through whole genome shotgun sequencing.
  • Generate 4X coverage of the Histoplasma capsulatum G186AR genome in addition to the existing 6X coverage and create a high quality assembly.
  • Perform automated annotation of the sequence assembly.
  • Distribute the sequence assembly and results of our annotation and analysis through a freely accessible, public web server at the Broad and by deposition of the sequence assembly in GenBank.

Data Releases

For Histoplasma capsulatum class NAmI strain WU24, we produced whole genome shotgun sequence from two plasmid libraries (4kb and 10kb inserts) and a Fosmid library. The resulting 7X assembly was made public in September 2005, and the results of automated genome annotation was made public May, 2006.

The Latin American Histoplasma capsulatum class H81 strain G186AR was assembled from sequence reads produced by both the Broad Institute and the Washington University School of Medicine. Sequences were obtained from 454 pOT library beads and fosmid libraries containing 3.1kb, 4.1kb, 5.7 kb, and 39kb inserts. The resulting 10X assembly was made public in May 2008 and the results of automated genome annotation will be made public in future releases.

For the Histoplasma capsulatum African clade (H143) strain, we produced whole genome shotgun sequence from a pOT (4kb insert) plasmid library, and a Fosmid library. For the Histoplasma capsulatum African clade (H88) strain, we produced whole genome shotgun sequence from two plasmid libraries (4kb and 10kb inserts) and a Fosmid library. The resulting 4X and 8X assemblies of each strain respectively, were made public in June 2008 and the results of automated genome annotations will be made public in future releases.

Questions about the project should be directed to annotation-webmaster@broad.mit.edu.

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, Kohler S, Schnizlein-Bick C, LeMonte A, Connolly P, Goldberg J, Garringer T, Wheat LJ. (2001) Chronic infection and reactivation in a pulmonary challenge model of histoplasmosis. J Infect Dis. 183(12):1822-4.

Kasuga T, White TJ, Koenig G, McEwen J, Restrepo A, Castaneda E, Da Silva Lacaz C, Heins-Vaccari EM, De Freitas RS, Zancope-Oliveira RM, Qin Z, Negroni R, Carter DA, Mikami Y, Tamura M, Taylor ML, Miller GF, Poonwan N, Taylor JW.(2003) Phylogeography of the fungal pathogen Histoplasma capsulatum. Mol Ecol. 12(12):3383-401.