title: Glycosylphosphatidylinositol (GPI) anchor is required in Aspergillus fumigatus for morphogenesis and virulence.
abstract: In yeast, glycosylphosphatidylinositol (GPI) is essential for viability and plays an important role in biosynthesis and organization of cell wall. Initiation of the GPI anchor biosynthesis is catalysed by the GPI-N-acetylglucosaminyltransferase complex (GPI-GnT). The GPI3 (SPT14) gene is thought to encode the catalytic subunit of GPI-GnT complex. In contrast to Saccharomyces cerevisiae, little is known about the GPI biosynthesis in filamentous fungi. In this study, the afpig-a gene was identified as the homologue of the GPI3/pig-A gene in Aspergillus fumigatus, an opportunistic fungal pathogen. By replacement of the afpig-a gene with a pyrG gene, we obtained the null mutants. Although the Deltaafpig-a mutant exhibited a significant increased cell lysis instead of temperature-sensitive or conditional lethal phenotype associated to the GPI3 mutant of yeast, they could survive at temperatures from 30 degrees C to 50 degrees C. The analysis of the mutants showed that a completely blocking of the GPI anchor synthesis in A. fumigatus led to cell wall defect, abnormal hyphal growth, rapid conidial germination and aberrant conidiation. In vivo assays revealed that the mutant exhibited a reduced virulence in immunocompromised mice. The GPI anchor was not essential for viability, but required for the cell wall integrity, morphogenesis and virulence in A. fumigatus.
authors.affiliation: State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, and The General Hospital of Chinese People's Armed Police Forces, Beijing 100080, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.forename: Yuanming
authors.initials: Y
authors.lastname: Luo
authors.forename: Haomiao
authors.initials: H
authors.lastname: Ouyang
authors.forename: Hongyan
authors.initials: H
authors.lastname: Hu
authors.forename: Cheng
authors.initials: C
authors.lastname: Jin
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity* / Q000502:physiology*; D002473:Cell Wall / Q000648:ultrastructure; D004195:Disease Models, Animal; D017353:Gene Deletion; D017261:Glycosylphosphatidylinositols / Q000096:biosynthesis* / Q000502:physiology; D006651:Histocytochemistry; D025301:Hyphae / Q000254:growth & development / Q000648:ultrastructure; D016867:Immunocompromised Host; D008168:Lung / Q000382:microbiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability / Q000235:genetics*; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013172:Spores, Fungal / Q000648:ultrastructure; D016019:Survival Analysis; D014774:Virulence / Q000235:genetics / Q000502:physiology
chemical_list: D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein