Microtubules and Actin Cytoskeleton of Potentially Pathogenic Basidiomycetous Yeast as Targets for Antifungals

Abstract

Background: The cytoskeleton was investigated as a potential target for the inhibition of cell division in Fellomyces fuzhouensis CBS 8243 related to Cryptococcus neoformans. Methods: Vincristine, vinblastine, paclitaxel, methyl benzimidazole-2-yl carbamate (BCM), thiabendazole, cytochalasins A, B and D and latrunculin A were added to yeast extract peptone dextrose medium containing cells, investigated by phase contrast and fluorescence microscopy, counted in a Bürker chamber and absorbance was measured. Results: Vincristine, vinblastine, paclitaxel, cytochalasins A, B and D transiently blocked proliferation. BCM disrupted microtubules and inhibited mitosis, but F-actin patches and cables persisted and neck-less conidia appeared without stalks. Latrunculin disrupted F-actin, cells became spherical, and stalks and necks degenerated; microtubules persisted, but mitosis, cytokinesis and conidiogenesis were blocked. The combined application of latrunculin and BCM disrupted F-actin and microtubules, and inhibited cells became spherical and did not divide. Conclusions: Microtubules and F-actin are effective targets for permanent inhibition of nuclear and cell division and conidiogenesis by BCM and latrunculin A.