title: Effects of Microtubule and Actin Inhibitors on Cryptococcus neoformans Examined by Scanning and Transmission Electron Microscopy.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Combined microtubule and actin inhibitors (VIN + LA or BCM + LA), have lethal effects on C. neoformans cells and no resistant cells originate.
authors.affiliation: Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Marie
authors.initials: M
authors.lastname: Kopecká
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors* / Q000648:ultrastructure; D001562:Benzimidazoles / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002219:Carbamates / Q000494:pharmacology*; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000648:ultrastructure; D006801:Humans; D008855:Microscopy, Electron, Scanning / Q000379:methods; D046529:Microscopy, Electron, Transmission / Q000379:methods*; D008870:Microtubules / Q000187:drug effects* / Q000648:ultrastructure; D053778:Thiazolidines / Q000494:pharmacology*; D016896:Treatment Outcome; D014750:Vincristine / Q000494:pharmacology*
chemical_list: D000199:Actins; D001562:Benzimidazoles; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002219:Carbamates; D053778:Thiazolidines; D014750:Vincristine; C006698:carbendazim; C037067:latrunculin A