title: Effects of micafungin on the morphology of Aspergillus fumigatus.
abstract: The morphological effects of micafungin, a member of a new class of antifungal agents candins, on growing hyphae of Aspergillus fumigatus were studied by the use of Nomarski microscopy, scanning electron microscopy and thin-section electron microscopy. Micafungin at concentrations of 0.001-0.1 microg ml(-1) strongly inhibited the in vitro growth of this fungus and induced striking changes in the hyphal morphology, depending on the drug concentration and the length of the incubation period. The changes observed included increased formation of branches on the lateral walls, disruption of the tips of both hyphal cells and branches, and crushing and collapse of whole hyphae. In addition, micafungin was also effective in damaging membranous structures, including disruption of the cell membrane, partial loss of nuclear membranes and expansion of endoplasmic reticula. From these results, it was concluded that micafungin primarily affected the normal formation of cell walls and septa of growing hyphae. The inhibition of apical growth of hyphae accompanied by excessive lateral branching that was followed by disruption of both hyphal tips and branch tips ultimately led to the destruction of whole hyphae. This cytological effect of micafungin on the hyphal growth of A. fumigatus can explain its potent anti-Aspergillus activity.
authors.affiliation: Teikyo University Institute of Medical Mycology, Hachioji, Tokyo 192-0395, Japan. ynishiya@main.teikyo-u.ac.jp
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Nishiyama
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Hasumi
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ueda
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Uchida
authors.forename: Hideyo
authors.initials: H
authors.lastname: Yamaguchi
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000254:growth & development / Q000648:ultrastructure*; D049108:Cell Enlargement / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002473:Cell Wall / Q000187:drug effects / Q000648:ultrastructure; D054714:Echinocandins; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000648:ultrastructure; D055666:Lipopeptides; D008074:Lipoproteins / Q000494:pharmacology*; D000077551:Micafungin; D008854:Microscopy, Electron; D010456:Peptides, Cyclic / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D000077551:Micafungin