latrunculin-a and carbendazim

Cryptococcus neoformans is one of the most important human fungal pathogens. Its cells contain rich microtubules required for nuclear division and rich F-actin cytoskeletons for cell division. Disruption of microtubules by a microtubule inhibitor should block nuclear division, and disruption of F-actin by an actin inhibitor should block cell division. We investigated the effects of microtubule and actin inhibitors to find out whether the cytoskeletons of C. neoformans can become a new anti-fungal target for the inhibition of cell division, when examined at the ultrastructural level.. Cells treated with the microtubule inhibitors vincristine (VIN) and methyl benzimidazole-2-ylcarbamate (BCM) and the actin inhibitor latrunculin A (LA), in yeast extract peptone dextrose medium, were examined by scanning (SEM) and transmission electron microscopy (TEM), and the cell number was counted using a Bürker chamber.. After 2 days of inhibition with VIN, BCM or LA, the cells did not divide, but later, resistant, proliferating cells appeared in all samples. With combined microtubule and actin inhibitors (VIN + LA or BCM + LA), cells did not divide during 6 or even 14 days, and no resistant cells originated. TEM showed that the inhibited cells were without cytoplasm and were dead; only empty cell walls persisted with reduced capsules, shown on SEM.. Combined microtubule and actin inhibitors (VIN + LA or BCM + LA), have lethal effects on C. neoformans cells and no resistant cells originate.

Topics: Actins; Benzimidazoles; Bridged Bicyclo Compounds, Heterocyclic; Carbamates; Cryptococcus neoformans; Humans; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Microtubules; Thiazolidines; Treatment Outcome; Vincristine

In most eukaryotes cytokinesis is brought about by a contractile actin ring located at the division plane. Here, in fission yeast the actin ring was found to be required to generate late-mitotic microtubular structures located at the division plane, and these in turn maintained the medial position of the actin ring. When these microtubular structures were disrupted, the actin ring migrated away from the cell middle in a membrane traffic-dependent manner, resulting in asymmetrical cell divisions that led to genomic instability. We propose that these microtubular structures contribute to a checkpoint control that retains the equatorial position of the ring when progression through cytokinesis is delayed.

Topics: Actins; Anaphase; Benzimidazoles; Bridged Bicyclo Compounds, Heterocyclic; Carbamates; Cell Cycle Proteins; Cell Division; Cell Nucleus; Cytoskeletal Proteins; Interphase; Microtubule-Organizing Center; Microtubules; Mitosis; Mutation; Recombinant Fusion Proteins; Schizosaccharomyces; Schizosaccharomyces pombe Proteins; Temperature; Thiazoles; Thiazolidines; Tubulin