Disruption of the Aspergillus fumigatus ECM33 homologue results in rapid conidial germination, antifungal resistance and hypervirulence.
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.
Romano
Jacob
J
Department of Human Microbiology, Sackler School of Medicine, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat-Aviv 69978, Tel-Aviv, Israel.
Nimrod
Guy
G
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat-Aviv 69978, Tel-Aviv, Israel.
Ben-Tal
Nir
N
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat-Aviv 69978, Tel-Aviv, Israel.
Shadkchan
Yona
Y
Department of Human Microbiology, Sackler School of Medicine, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat-Aviv 69978, Tel-Aviv, Israel.
Baruch
Koti
K
Department of Human Microbiology, Sackler School of Medicine, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat-Aviv 69978, Tel-Aviv, Israel.
Sharon
Haim
H
Department of Human Microbiology, Sackler School of Medicine, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat-Aviv 69978, Tel-Aviv, Israel.
Osherov
Nir
N
Department of Human Microbiology, Sackler School of Medicine, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat-Aviv 69978, Tel-Aviv, Israel.
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
D054714:Echinocandins; D005656:Fungal Proteins; D055666:Lipopeptides; D010456:Peptides, Cyclic; D003224:Congo Red; D000077336:Caspofungin