Abstract
In fungi many proteins, which play important roles in maintaining the function of the cell wall and participating in pathogenic processes, are anchored to the cell surface by a glycosylphosphatidylinositol (GPI) anchor. It has been known that modification and removal of phosphoethanolamine (EtN-P) on the second mannose residue in GPI anchors is important for maturation and sorting of GPI anchored proteins in yeast and mammalian cells, but is a step absent from some protist parasites. In Aspergillus fumigatus, an opportunistic fungal pathogen causing invasive aspergillosis in humans, GPI-anchored proteins are known to be involved in cell wall synthesis and virulence. In this report the gene encoding A. fumigatus EtN-P transferase GPI7 was investigated. By deletion of the gpi7 gene, we evaluated the effects of EtN-P modification on the morphogenesis of A. fumigatus and localization of GPI proteins. Our results showed that deletion of the gpi7 gene led to reduced cell membrane GPI anchored proteins, the mis-localization of the cell wall GPI anchored protein Mp1, abnormal polarity, and autophagy in A. fumigatus. Our results suggest that addition of EtN-P of the second mannose on the GPI anchor is essential for transportation and localization of the cell wall GPI-anchored proteins.
Highlights
Species belonging to Aspergillus, Candida, Cryptococcus, and Pneumocystis are major fungal pathogens causing invasive infections among immunocompromised patients
Genes required for the attachment of the EtN-P have been identified in yeast and human cell: PIG-N/MCD4 are responsible for the transfer of EtN-P onto the first mannose residue of GPI anchor, GPI7 transfers EtN-P onto the second mannose residue, and PIG-O/GPI13 transfer EtN-P onto the third mannose residue
We demonstrated that deletion of the gpi[7] in A. fumigatus led to abnormal polarity, altered levels of plasma membrane GPI-anchored proteins (GPI-PMP), mislocalization of cell wall GPI anchor proteins (GPI-CWP), and autophagy
Summary
Species belonging to Aspergillus, Candida, Cryptococcus, and Pneumocystis are major fungal pathogens causing invasive infections among immunocompromised patients. Aspergillus fumigatus is the second clinically important fungal pathogen, accounts for about 65% of all invasive infections in humans and is the mostly encountered species in pulmonary infections[3]. It has been shown that efficient internalization of conidia by epithelial cells, delayed germination, and hyphal growth parallel to the epithelium might be the causes for the success of A. fumigatus[8]. All these abilities can contribute to the survival of A. fumigatus inside the human body, www.nature.com/scientificreports/. It has been shown that suppression of the GPI anchor biosynthesis leads to a defect in cell wall and increased cell death in A. fumigatus[11]. In T. cruzi, T. brucei and P. falciparum, only the third mannose is modified by EtNP and only GPI13 homologues are found[18]
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