Electron microscopic studies on the mechanism of action of clotrimazole onCanada albicans

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Abstract
During investigations on the mechanism of action of clotrimazole, electron microscopy was undertaken. When Candida albicans cells were exposed to a fungistatic concentration (3 × 10-5 M) of the drug, there was no cytological change except the swelling of mitochondria. Exposure to a fungicidal level (1.5 × 10-4 M) produced unusual development and destruction of certain membranous structures. The cell membrane frequently invaginated to form extensive and complex intracytoplasmic membranes varying in size, shape and complexity. Such structures were usually close to vacuoles. Numerous membrane particles occurred between the retracted cell membrane and the cell wall (lomasomes). In contrast, the nuclear membrane as well as the mitochondrial inner membrane deteriorated markedly. Intracytoplasmic vacuoles increased in size and number and, often contained multivesicular structures. Plasmolysis, accompanied by complete disorganization of cytoplasmic structures, appears to be the terminal event. The nature and the interval before onset of these cytological changes produced by the fungicidal level of the drug were correlated with the time-dependent effect on cell viability and membrane permeability.