ULTRASTRUCTURAL INVESTIGATIONS OF CANDIDA-ALBICANS AFTER IN-VITRO TREATMENT WITH THE NEW FUNGICIDAL AGENT RILOPIROX

Candida albicans was maintained in various culture media and incubated with different concentrations of the antifungal agent rilopirox. Afte r fixation, dehydration and embedding in Spurr's medium, the cells wer e analysed at the ultrastructural level to investigate morphological a spects of the antifungal mode of action of this new hydroxypyridone co mpound. All untreated or sham-treated control cells exhibited a normal ultrastructural appearance. The cells were surrounded by a multilayer ed cell wall of typical structure, and the plasmalemma was in close co ntact with the cell wall. Also, the cell organelles of the protoplast corresponded well with the findings of other authors. After treatment with rilopirox, a variety of ultrastructural changes were seen, and th e extent of damage was dependent on the specific culture condition, dr ug concentration and incubation time. After only 6 h and 1-10 mug ml-1 rilopirox, the plasmalemma exhibited elongated invaginations, the num ber and size of the lipid droplets had increased and greatly enlarged mitochondria containing electron-dense deposits became visible. The va cuolar system was strongly expanded and occupied nearly the whole cell . Exposure to higher concentrations of the antifungal agent and prolon ged incubation times resulted in complete cytoplasmic autolysis and me mbrane breakdown, while the fungal cell wall remained unaffected. Afte r treatment with 0.5% rilopirox suspension gel on agar cultures, the e xtent of cellular damage was clearly enhanced and included all cell ty pes of a treated yeast colony, i.e. single blastospores and pseudohyph ae.