Vesicular transport in Histoplasma capsulatum: an effective mechanism for trans-cell wall transfer of proteins and lipids in ascomycetes.
Vesicular secretion of macromolecules has recently been described in the basidiomycete Cryptococcus neoformans, raising the question as to whether ascomycetes similarly utilize vesicles for transport. In the present study, we examine whether the clinically important ascomycete Histoplasma capsulatum produce vesicles and utilized these structures to secrete macromolecules. Transmission electron microscopy (TEM) shows transcellular secretion of vesicles by yeast cells. Proteomic and lipidomic analyses of vesicles isolated from culture supernatants reveal a rich collection of macromolecules involved in diverse processes, including metabolism, cell recycling, signalling and virulence. The results demonstrate that H. capsulatum can utilize a trans-cell wall vesicular transport secretory mechanism to promote virulence. Additionally, TEM of supernatants collected from Candida albicans, Candida parapsilosis, Sporothrix schenckii and Saccharomyces cerevisiae documents that vesicles are similarly produced by additional ascomycetes. The vesicles from H. capsulatum react with immune serum from patients with histoplasmosis, providing an association of the vesicular products with pathogenesis. The findings support the proposal that vesicular secretion is a general mechanism in fungi for the transport of macromolecules related to virulence and that this process could be a target for novel therapeutics.
Albuquerque
Priscila Costa
PC
Instituto de Pesquisa Clinica Evandro Chagas, Fundação Oswaldo Cruz, RJ Brazil.
Nakayasu
Ernesto S
ES
Rodrigues
Marcio L
ML
Frases
Susana
S
Casadevall
Arturo
A
Zancope-Oliveira
Rosely M
RM
Almeida
Igor C
IC
Nosanchuk
Joshua D
JD
D001692:Biological Transport / Q000235:genetics; D002473:Cell Wall / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism*; D006658:Histoplasma / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure*; D006660:Histoplasmosis / Q000276:immunology / Q000382:microbiology; D054884:Host-Pathogen Interactions; D050356:Lipid Metabolism; D046529:Microscopy, Electron, Transmission; D010743:Phospholipids / Q000032:analysis / Q000378:metabolism; D022142:Secretory Vesicles / Q000737:chemistry* / Q000378:metabolism
D005656:Fungal Proteins; D010743:Phospholipids