Histoplasma capsulatum Molecular Genetics, Pathogenesis, and Responsiveness to Its Environment

Woods, Jon P.

doi:10.1006/fgbi.2001.1311

Cited by 84 publications

(63 citation statements)

References 131 publications

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“…C. posadasii is a highly virulent species that can cause serious, sometimes fatal, systemic infections (Fisher et al, 2002;Kirkland & Fierer, 1996). H. capsulatum is a common cause of respiratory tract infections, and can be lifethreatening (Woods, 2002). C. neoformans is an important opportunistic pathogen of humans that poses a significant threat to immunocompromised individuals (Kwon-Chung & Bennett, 1992).…”

Section: Introductionmentioning

confidence: 99%

Cryptons: a group of tyrosine-recombinase-encoding DNA transposons from pathogenic fungi

2003

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A new group of transposable elements, which the authors have named cryptons, was detected in several pathogenic fungi, including the basidiomycete Cryptococcus neoformans, and the ascomycetes Coccidioides posadasii and Histoplasma capsulatum. These elements are unlike any previously described transposons. An archetypal member of the group, crypton Cn1, is 4 kb in length and is present at a low but variable copy number in a variety of C. neoformans strains. It displays interstrain variations in its insertion sites, suggesting recent mobility. The internal region contains a long gene, interrupted by several introns. The product of this gene contains a putative tyrosine recombinase near its middle, and a region similar in sequence to the DNA-binding domains of several fungal transcription factors near its C-terminus. The element contains no long repeat sequences, but is bordered by short direct repeats which may have been produced by its insertion into the host genome by recombination. Many of the structural features of crypton Cn1 are conserved in the other known cryptons, suggesting that these elements represent the functional forms. The presence of cryptons in ascomycetes and basidiomycetes suggests that this is an ancient group of elements (>400 million years old). Sequence comparisons suggest that cryptons may be related to the DIRS1 and Ngaro1 groups of tyrosine-recombinaseencoding retrotransposons.

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Section: Introductionmentioning

confidence: 99%

Cryptons: a group of tyrosine-recombinase-encoding DNA transposons from pathogenic fungi

2003

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“…This phenomenon has allowed the identification of genes that are differentially expressed in response to temperature (11)(12)(13), but much remains to be discovered about the regulatory factors that allow the cells to sense and respond to temperature appropriately. Here, we use insertional mutagenesis to identify RYP1, a critical regulator of yeast-phase growth.…”

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confidence: 99%

Temperature-induced switch to the pathogenic yeast form of Histoplasma capsulatum requires Ryp1, a conserved transcriptional regulator

Nguyen

Sil

2008

Proc. Natl. Acad. Sci. U.S.A.

174

207

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Histoplasma capsulatum, a fungal pathogen of humans, switches from a filamentous spore-forming mold in the soil to a pathogenic budding-yeast form in the human host. This morphologic switch, which is exhibited by H. capsulatum and a group of evolutionarily related fungal pathogens, is regulated by temperature. Using insertional mutagenesis, we identified a gene, RYP1 (required for yeast phase growth), which is required for yeast-form growth at 37°C. ryp1 mutants are constitutively filamentous irrespective of temperature. Ryp1 is a member of a family of fungal proteins that includes Wor1, a master transcriptional regulator of the whiteopaque transition required for mating in Candida albicans. Ryp1 associates with its own upstream regulatory region, consistent with a direct role in transcriptional control, and both the protein and its transcript accumulate to high levels in wild-type yeastphase cells. Microarray analysis demonstrated that Ryp1 is required for the expression of the vast majority of yeast-specific genes, including two genes linked to virulence. Thus, Ryp1 appears to be a critical transcriptional regulator of a temperature-regulated morphologic switch in H. capsulatum.fungal pathogenesis ͉ gene regulation ͉ morphology

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“…Histoplasma infection commonly results in mild or unapparent clinical symptoms in immune-competent individuals and is endemic throughout large areas of the American Midwest (5). However, in immune-compromised individuals deficient in CD4 ϩ T cell function, failure of adequate granuloma function allows the fungus to disseminate systemically and can lead to a serious, life-threatening disease course (6,7).…”

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confidence: 99%

Characterization of theHistoplasma capsulatum-Induced Granuloma

Héninger

Hogan²,

Karman

et al. 2006

The Journal of Immunology

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Rising rates of Histoplasma capsulatum infection are an emerging problem among the rapidly growing population of immune-compromised individuals. Although there is a growing understanding of systemic immunity against Histoplasma, little is known about the local granulomatous response, which is an important component in the control of infection. The focus of this article is the characterization of Histoplasma-induced granulomas. Five days after i.p. infection, infected macrophage appear in the liver and lung; however, no granulomas are apparent. Two days later, well-formed sarcoid granulomas are abundant in the lung and liver of infected mice, which contain all visible Histoplasma. Granulomas are dominated by macrophage and lymphocytes. Most of the Histoplasma and most of the apoptotic cells are found in the center of the lesions. We isolated liver granulomas at multiple time points after infection and analyzed the cellular composition, TCR gene usage, and cytokine production of granuloma-infiltrating cells. The lesions contain both CD4+ and CD8+ T cell subsets, and T cells are the primary source of IFN-γ and IL-17. The main source of local TNF-α is macrophage. Chemokines are produced by both infiltrating macrophage and lymphocytes. Dendritic cells are present in granulomas; however, T cell expansion seems to occur systemically because TCR usage is very heterogeneous even at the level of individual lesions. This study is the first direct examination of host cellular responses in the Histoplasma-induced granuloma representing the specific interface between host and pathogen. Our studies will allow further analysis of key elements of host Histoplasma interactions at the site of chronic infection.

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Histoplasma capsulatum Molecular Genetics, Pathogenesis, and Responsiveness to Its Environment

Cited by 84 publications

References 131 publications

Cryptons: a group of tyrosine-recombinase-encoding DNA transposons from pathogenic fungi

Cryptons: a group of tyrosine-recombinase-encoding DNA transposons from pathogenic fungi

Temperature-induced switch to the pathogenic yeast form of Histoplasma capsulatum requires Ryp1, a conserved transcriptional regulator

Characterization of theHistoplasma capsulatum-Induced Granuloma

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