Vesicular Trans-Cell Wall Transport in Fungi: A Mechanism for the Delivery of Virulence-Associated Macromolecules?

Abstract

Fungal cells are encaged in rigid, complex cell walls. Until recently, there was remarkably little information regarding the trans-fungal cell wall transfer of intracellular macromolecules to the extracellular space. Recently, several studies have begun to elucidate the mechanisms that fungal cells utilize to secrete a wide variety of macromolecules through the cell wall. The combined use of transmission electron microscopy, serology, biochemistry, proteomics and lipidomics have revealed that the fungal pathogens Cryptococcus neoformans, Histoplasma capsulatum, Candida albicans, Candida parapsilosis and Sporothrix schenckii, as well as the model yeast Saccharomyces cerevisiae, each produces extracellular vesicles that carry lipids, proteins, polysaccharides and pigment-like structures of unquestionable biological signifi cance. Compositional analysis of the C. neoformans and H. capsulatum extracellular vesicles suggests that they may function as 'virulence bags', with the potential to modulate the host-pathogen interaction in favor of the fungus. The cellular origin of the extracellular vesicles remains unknown, but morphological and biochemical features indicate that they are similar to the well-described mammalian exosomes.

Immunoproteomics and Immunoinformatics Analysis of Cryptococcus Gattii : Novel Candidate Antigens for Diagnosis

“…Such proteins have previously been identified as being essential for intracellular survival, virulence and resistance to oxidative and nitrosative stress in C. neoformans, as reported by Missall et al [63][64][65] and Wang et al [66]. The finding presented here that thiol peroxidase is an antigenic target in C. gattii genotype VGII corroborates the findings of Jobbins et al [56] and supports the hypothesis that this protein is involved in the pathogenesis of C. gattii genotype VGII infection in humans [62,[67][68][69].…”

Vesicular Transport Systems in Fungi

“…Secondly, trans-cell wall vesicular release could be a more general mechanism used by other fungi for macromolecular export. The morphological similarity between fungal vesicles and mammalian exosomes [13,15,16,39] also raised questions on their mechanisms of biogenesis. Thirdly, depending on their molecular composition, extracellular vesicles could be immunologically active, as well characterized for bacterial vesicles [10,40] and mammalian exosomes [41].…”

“…For H. capsulatum , C. neoformans and S. cerevisiae , protein components of extracellular vesicles were characterized by proteomic approaches [13,14,23]. These analyses revealed a great compositional diversity, which included the characterization of a number of proteins of different cellular classes.…”

Sporothrix schenckii and Sporotrichosis

“…The fungal cell wall is rigid as well as complex, and recently it has been shown that S. schenckii produces vesicles that are probably related to the transfer of periplasmic molecules and pigment-like structures from the plasma membrane to the extracellular space, since in contrast to the case for prokaryotic organisms, in eukaryotic cells there is vesicular traffic of molecules to the plasma membrane (3,197).…”