title: Disruption of the Aspergillus fumigatus ECM33 homologue results in rapid conidial germination, antifungal resistance and hypervirulence.
abstract: The ECM33/SPS2 family of glycosylphosphatidylinositol-anchored proteins plays an important role in maintaining fungal cell wall integrity and virulence. However, the precise molecular role of these proteins is unknown. In this work, AfuEcm33, the gene encoding the ECM33 homologue in the important pathogenic fungus Aspergillus fumigatus, has been cloned and its function analysed. It is shown that disruption of AfuEcm33 results in rapid conidial germination, increased cell-cell adhesion, resistance to the antifungal agent caspofungin and increased virulence in an immunocompromised mouse model for disseminated aspergillosis. These results suggest that the protein encoded by AfuEcm33 is involved in key aspects of cell wall morphogenesis and plays an important role in A. fumigatus virulence.
authors.affiliation: Department of Human Microbiology, Sackler School of Medicine, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat-Aviv 69978, Tel-Aviv, Israel.
authors.forename: Jacob
authors.initials: J
authors.lastname: Romano
authors.affiliation: Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat-Aviv 69978, Tel-Aviv, Israel.
authors.forename: Guy
authors.initials: G
authors.lastname: Nimrod
authors.affiliation: Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat-Aviv 69978, Tel-Aviv, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Ben-Tal
authors.affiliation: Department of Human Microbiology, Sackler School of Medicine, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat-Aviv 69978, Tel-Aviv, Israel.
authors.forename: Yona
authors.initials: Y
authors.lastname: Shadkchan
authors.affiliation: Department of Human Microbiology, Sackler School of Medicine, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat-Aviv 69978, Tel-Aviv, Israel.
authors.forename: Koti
authors.initials: K
authors.lastname: Baruch
authors.affiliation: Department of Human Microbiology, Sackler School of Medicine, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat-Aviv 69978, Tel-Aviv, Israel.
authors.forename: Haim
authors.initials: H
authors.lastname: Sharon
authors.affiliation: Department of Human Microbiology, Sackler School of Medicine, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat-Aviv 69978, Tel-Aviv, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Osherov
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000209:etiology; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity*; D000077336:Caspofungin; D002473:Cell Wall / Q000187:drug effects; D003224:Congo Red / Q000494:pharmacology; D025141:Drug Resistance, Fungal; D054714:Echinocandins; D005260:Female; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D055666:Lipopeptides; D051379:Mice; D008813:Mice, Inbred ICR; D009024:Morphogenesis; D010456:Peptides, Cyclic / Q000494:pharmacology; D014774:Virulence
chemical_list: D054714:Echinocandins; D005656:Fungal Proteins; D055666:Lipopeptides; D010456:Peptides, Cyclic; D003224:Congo Red; D000077336:Caspofungin