Intracellular Parasitism by Histoplasma capsulatum: Fungal Virulence and Calcium Dependence

Science ◽  
2000 ◽  
Vol 290 (5495) ◽  
pp. 1368-1372 ◽  
Author(s):  
T. S. Sebghati
Keyword(s):  
Histoplasma Capsulatum ◽  
Fungal Virulence ◽  
Calcium Dependence

scholarly journals Cbp1, a rapidly evolving fungal virulence factor, forms an effector complex that drives macrophage lysis

2021 ◽  
Author(s):  
Dinara Azimova ◽  
Nadia Herrera ◽  
Lucian Duvenage ◽  
Mark Voorhies ◽  
Bevin C English ◽  
...  
Keyword(s):  
Host Cell ◽  
Virulence Factor ◽  
Calcium Binding ◽  
Fungal Pathogen ◽  
Histoplasma Capsulatum ◽  
De Novo ◽  
Subcellular Fractionation ◽  
Host Cells ◽  
Yeast Cells ◽  
Fungal Virulence

Intracellular pathogens secrete effectors to manipulate their host cells. Histoplasma capsulatum (Hc) is a fungal intracellular pathogen of humans that grows in a yeast form in the host. Hc yeasts are phagocytosed by macrophages, where fungal intracellular replication precedes macrophage lysis. The most abundant virulence factor secreted by Hc yeast cells is Calcium Binding Protein 1 (Cbp1), which is absolutely required for macrophage lysis. Here we take an evolutionary, structural, and cell biological approach to understand Cbp1 function. We find that Cbp1 is present only in the genomes of closely related dimorphic fungal species of the Ajellomycetaceae family that lead primarily intracellular lifestyles in their mammalian hosts (Histoplasma, Paracoccidioides, and Emergomyces), but not conserved in the extracellular fungal pathogen Blastomyces dermatitidis. We determine the de novo structures of Hc H88 Cbp1 and the Paracoccidioides americana (Pb03) Cbp1, revealing a novel 'binocular' fold consisting of a helical dimer arrangement wherein two helices from each monomer contribute to a four-helix bundle. In contrast to Pb03 Cbp1, we show that Emergomyces Cbp1 orthologs are unable to stimulate macrophage lysis when expressed in the Hc cbp1 mutant. Consistent with this result, we find that wild-type Emergomyces africanus yeast are able to grow within primary macrophages but are incapable of lysing them. Finally, we use subcellular fractionation of infected macrophages and indirect immunofluorescence to show that Cbp1 localizes to the macrophage cytosol during Hc infection, making this the first instance of a phagosomal human fungal pathogen directing an effector into the cytosol of the host cell. We additionally show that Cbp1 forms a complex with Yps-3, another known Hc virulence factor that accesses the cytosol. Taken together, these data imply that Cbp1 is a rapidly evolving fungal virulence factor that localizes to the cytosol to trigger host cell lysis.

Recognition of Fungal Components by the Host Immune System

2020 ◽  
Vol 21 (3) ◽  
pp. 245-264 ◽  
Author(s):  
Laura C. García-Carnero ◽  
José A. Martínez-Álvarez ◽  
Luis M. Salazar-García ◽  
Nancy E. Lozoya-Pérez ◽  
Sandra E. González-Hernández ◽  
...  
Keyword(s):  
Immune System ◽  
Histoplasma Capsulatum ◽  
Paracoccidioides Brasiliensis ◽  
Sporothrix Schenckii ◽  
Clinical Importance ◽  
Pathogenic Fungi ◽  
Diagnostic Tools ◽  
Future Research ◽  
Host Immune System ◽  
Fungal Antigens

: By being the first point of contact of the fungus with the host, the cell wall plays an important role in the pathogenesis, having many molecules that participate as antigens that are recognized by immune cells, and also that help the fungus to establish infection. The main molecules reported to trigger an immune response are chitin, glucans, oligosaccharides, proteins, melanin, phospholipids, and others, being present in the principal pathogenic fungi with clinical importance worldwide, such as Histoplasma capsulatum, Paracoccidioides brasiliensis, Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans, Blastomyces dermatitidis, and Sporothrix schenckii. Knowledge and understanding of how the immune system recognizes and responds to fungal antigens are relevant for the future research and development of new diagnostic tools and treatments for the control of mycosis caused by these fungi.

Germination of the Macroconidium of Histoplasma Capsulatum

Mycologia ◽  
1964 ◽  
Vol 56 (5) ◽  
pp. 662-671 ◽  
Author(s):  
Roger D. Goos
Keyword(s):  
Histoplasma Capsulatum
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