Morphological changes of Candida albicans induced by BMY-28864, a highly water-soluble pradimicin derivative.
The time course of BMY-28864-dependent morphological changes in Candida albicans A9540 was studied by electron microscopy. Scanning electron microscopy revealed that BMY-28864 often induced cell surface deformations such as abnormal swelling and bulging around budding sites and bud scars. The cell membrane damage was visualized by freeze-fracturing technique as deep pit-like invaginations. Transmission electron microscopy with thin-sectioned specimens also demonstrated that BMY-28864 induced cell membrane invaginations together with cell membrane detachment from the cell wall, nuclear membrane fragmentation and mitochondrial aberration. Statistical sequence analysis of the prominent BMY-28864-dependent morphological changes of the yeast cells led to the conclusion that BMY-28864 first attacked the cell membrane and then caused disintegration of other intracytoplasmic organelles, resulting in the lethal effect.
Numata
K
K
Bristol-Myers Squibb Research Institute, Bristol-Myers Squibb K.K., Tokyo, Japan.
Ueki
T
T
Naito
N
N
Yamada
N
N
Kamasawa
N
N
Oki
T
T
Osumi
M
M
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000648:ultrastructure*; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D005614:Freeze Fracturing; D008854:Microscopy, Electron / Q000379:methods*; D008855:Microscopy, Electron, Scanning; D008933:Mitochondrial Swelling / Q000187:drug effects; D009685:Nuclear Envelope / Q000187:drug effects / Q000648:ultrastructure; D012995:Solubility; D014867:Water; D000095643:Pradimicins and Benanomicins
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000935:Antifungal Agents; D014867:Water; C058036:pradimicin A; D000095643:Pradimicins and Benanomicins; C067714:N,N-dimethylpradimicin FA-2